Prostaglandins in non-insectan invertebrates: recent insights and unsolved problems
1 School of Biological Sciences, University of Wales Swansea, Singleton
Park, Swansea SA2 8PP, UK
2 Proteomics Section, Imperial College, Faculty of Medicine, London W12 0NN,
UK
3 School of Marine Science and Technology, University of Newcastle upon
Tyne, Newcastle NE1 7RU, UK
* Author for correspondence (e-mail: a.f.rowley{at}swansea.ac.uk)
Accepted 6 September 2004
![]() |
Summary |
---|
Prostaglandins in invertebrates can be categorised into two main types; the classical forms, such as PGE2 and PGD2 that are found in mammals, and novel forms including clavulones, bromo- and iodo-vulones and various PGA2 and PGE2 esters. A significant number of reports of PG identification in invertebrates have relied upon methods such as enzyme immunoassay that do not have the necessary specificity to ensure the validity of the identification. For example, in the barnacle Balanus amphitrite, although there are PG-like compounds that bind to antibodies raised against PGE2, mass spectrometric analysis failed to confirm the presence of this and other classical PGs. Therefore, care should be taken in drawing conclusions about what PGs are formed in invertebrates without employing appropriate analytical methods. Finally, the recent publication of the Ciona genome should facilitate studies on the nature and mode of biosynthesis of PGs in this advanced deuterostomate invertebrate.
Key words: barnacle, coral, cyclooxygenase, eicosanoid, leukotriene, prostaglandin, prostaglandin D synthase, tunicate, Ciona intestinalis, Balanus amphitrite.
![]() |
Introduction |
---|
Prostaglandins (PGs) were first discovered in the 1930s by von Euler and
colleagues, who found a substance produced by the prostate gland that caused
smooth muscle contraction. They christened the active substance
`prostaglandin', but it was over 30 years until the structure and mode of
biosynthesis of these fatty acid derivatives became fully understood. PGs have
many basic physiological functions where they act as `local' hormones. For
example, thromboxane (Tx) A2 and prostacyclin (PGI2)
generated by platelets and endothelial cells, respectively, regulate the
aggregatory behaviour of platelets during haemostatic episodes
(Moncada and Vane, 1979).
Other PGs, including PGD2 and PGE2, are regulators of
sleep-wake activity in mammals (Hayaishi
2000
). For instance, in rat models, infusion of PGD2
specifically increases the duration of sleep in a dose-dependent way
(Hayaishi et al., 1990
).
PGE2 also influences the central nervous system (CNS) in terms of
temperature regulation, in which it acts as an endogenous pyrogen (see review
by DuBois et al., 1998
).
Several PGs target smooth muscle cells, causing their contraction or
relaxation. This is of particular importance in parturition where
PGF2
is an activator of myometrial contraction and cervical
ripening (Johnson and Everitt,
2000
). In the kidney PGs, including PGE2 and
PGI2, modulate haemodynamics as a result of their vasodilatory
activity and also have an effect on both salt and water balance
(DuBois et al., 1998
;
Frolich and Stichtenoth,
1998
). Finally, PGs play a complex role in inflammation, not only
in the early stages as pro-inflammatory mediators but also at a later stage in
eliciting resolution (Colville-Nash and
Gilroy, 2000
).
Aquatic invertebrates have played significant roles in our understanding of
the biological activities of PGs. In 1969, Weinheimer and Spraggins discovered
that one species of coral (Plexaura homomalla) contains up to 8% of
its dry mass as PG esters. For a short time, in the absence of other available
routes to synthesize PGs, this coral provided a ready source of precursors for
the synthesis of such compounds for use in studies with humans and other
mammalian models. From the many studies that have followed over the last 30
years, it is apparent that PGs play important roles in reproduction, ion
transport and defence across a wide range of invertebrates (reviewed in
Stanley, 2000). For instance,
in insects detailed research has revealed that PGs function in egg laying,
immune defence mechanisms and chloride transport (see reviews by
Stanley-Samuelson, 1990; Stanley and
Miller, 1998
; Stanley,
2000
). Despite a growing understanding of the roles of PGs in
invertebrates (reviewed by Stanley,
2000
), the nature of the products formed and their mode of
biosynthesis are still largely unknown, particularly in non-insectan forms.
This account therefore focuses on these aspects of PG biology and reviews some
recent findings from aquatic invertebrates including corals, barnacles and
tunicates. It questions whether all of the reports of PG identification and
presence in invertebrates are valid in light of these recent findings.
![]() |
Prostanoid biosynthetic pathways in mammals |
---|
|
As can be seen from Fig. 1,
the ultimate product of COX activity, PGH2, is subject to further
conversion to give rise to the generation of `classical' PGs including
PGD2, PGE2, PGF2 and PGI2
(prostacyclin) as well as TxA2. For such generation to occur,
further enzyme activity is usually required. For example, PGD synthases,
responsible for the generation of PGD2 from arachidonate, consist
of at least two evolutionarily distinct enzymes: a haemopoietic form expressed
in mast cells, Th2 lymphocytes and platelet precursors, and a lipocalin-type
PGD synthase found in the brain, testes and heart
(Urade and Eguchi, 2002
). The
haemopoietic form of PGD synthase is a member of the sigma-class glutathione
S-transferase family that has widespread distribution in
multicellular organisms (Thomson et al.,
1998
). PGE synthases also consist of both membrane-associated and
cytosolic forms (Murakami et al.,
2002
). The dramatic increase in PGE2 generation in some
inflammatory states appears to result from the induction of one of the
membrane-associated PGE synthases (termed mPGES-1), and the stimuli
responsible for the induction of COX-2 expression also induce the expression
of this type of PGE synthase (Reddy and
Herschman, 1997
; Mancini et
al., 2001
; Umatsu et al.,
2002
). The recent addition of a second membrane-associated form of
PGE synthase (mPGES-2) that is linked to both COX-1 and COX-2
(Murakami et al., 2003
)
emphasises the potential complexity of the relationship between PGE synthases
and COX-1 and COX-2. Various cytosolic glutathione S-transferases
also have the ability to convert PGH2 to PGE2 and other
PGs (Ujihara et al., 1988
).
Finally, TxA and PGI synthases are distinct members of the diverse cytochrome
P450 superfamily (Hara
et al., 1994
; Ullrich et al.,
2001
; Wang and Kulmacz,
2002
).
As well as the `classical' PGs, mention should be made of several
additional forms including PGA2, PGB2 and
PGJ2. The J-type PGs are unusual in that they contain a
cyclopentenone ring. PGD2 is the precursor for the non-enzymatic
generation of PGJ2 and related forms such as
12-PGJ2 and
15-deoxy-
12,14-PGJ2
(Hirata et al., 1988
).
PGA2 (also called medullin) is a non-enzymatic dehydration product
of PGE2, although the extent of its generation and biological
activity in mammals remains unclear.
Following their biosynthesis, PGs are exported from cells across the cell
membrane and bind to specific receptors on target cells. They can also be
carried across membranes by a PG transporter (PGT;
Kanai et al., 1995;
Pucci et al., 1999
). The
finding that PGT is expressed in cell types that synthesize and release PGs
may suggest that the transporter is involved in the re-uptake of PGs, either
as a way of negating their leakage and/or facilitating the transport of such
molecules to target nuclear receptors (Bao et al., 2002).
Our understanding of the nature and diversity of prostanoid receptors has
increased dramatically in the last two decades. Each of the main type of
prostanoid has its own specific G protein-coupled receptor. These are
classified into five types termed EP, DP, FP, IP and TP, corresponding to the
main prostanoids, PGE, PGD, PGF, PGI and TxA, respectively
(Tsuboi et al., 2002).
According to Tsuboi et al.
(2002
) with the exception of
the EP receptors, all the others consist of a single type. The EP receptors
for PGE consist of four main sub-types, EP1-EP4, in
which each has a distinctive structure, signalling pathway and tissue
distribution (Wright et al.,
2001
). The terminal product of PGD2 breakdown, namely
15-deoxy-
12,14-PGJ2, has its own specific nuclear
receptor, the
form of the peroxisome proliferator-activated receptor
(PPAR
). This receptor is an important regulator of adipocyte
differentiation (Negishi and Katoh,
2002
).
![]() |
Evidence for prostanoid generation in non-insectan invertebrates |
---|
|
As can be seen from Table 1,
the PGs formed in invertebrates appear to fall into two categories, namely
novel PGs only found in invertebrates, and the classical PGs (e.g.
PGE2, PGD2 etc.) found in both invertebrates and
vertebrates. The early studies of Weinheimer and Spraggins
(1969) with the coral P.
homomalla not only noted the unusual stereochemistry of the PGs formed
(R rather than the S forms found in vertebrates) but also
made the important finding that rather than the classical PGs, the main
products synthesized were esters of PGA2 and PGE2
(Fig. 2). Subsequently, a
number of other novel PGs have been reported from a diverse range of
cnidarians and sponges including chloro-, bromo- and iodo-vulones, clavulones,
punaglandins and mucosin (Table
1; Fig. 2). Several
of these products have received much attention due to their potential
antitumour activity (e.g. Iguchi et al.,
1985
,
1986
;
Honda et al., 1988
;
Iwashima et al., 1999
). Their
functional significance in the animals producing such compounds is unclear,
but they may provide defence against predation by fish
(Gerhart, 1991
) as well as
protecting against microbial attack
(
ezanka and Dembitsky,
2003
). Their potential as anti-predatory factors has, however,
been questioned (Pawlik and Fenical,
1989
) and further experimental work is required to confirm the
original observations.
|
One of the most impressive series of studies on PG biosynthesis in
invertebrates comes from the work on the opistobranch mollusc, Tethrys
fimbria (Cimino et al.,
1989,
1991a
,b
;
Di Marzo et al., 1991
). These
authors showed conclusively that this mollusc generates novel PG derivatives,
the PG 1,15-lactones, apparently derived from PGE2 and
PGF2
. The product profile in T. fimbriae also
differs between the mantle, cerata and reproductive glands
(Cimino et al., 1991b
;
Di Marzo et al., 1991
), with
PGs formed in the mantle exported to the cerata and reproductive glands where
further structural modification occurs. This regional-specific generation of
PGs may imply that these products perform different functions such as defence
in the cerata, and control of the reproductive processes in the ovary/testis
(Di Marzo et al., 1991
).
Because these studies have fully characterised the products formed and their
mode of biosynthesis, T. fimbria would make a good model for detailed
investigations aimed to determine the functional significance and mechanism of
action of the PGs formed.
As can be seen from Table 1,
there are many reports of the generation of classical PGs, particularly
PGE2, PGD2 and PGF2, in invertebrates.
A significant number of these have employed techniques such as enzyme
immunoassay (EIA), radioimmunoassay (RIA) and thin layer chromatography (TLC)
that alone do not provide the specificity to confidently report on the
presence of absence of various PGs. For instance, Knight et al.
(1999
) used commercially
available EIA kits to determine if PGE and PGF immunoreactivity was formed in
ionophore-challenged tissues from the tunicate, Ciona intestinalis.
Because this approach without HPLC or some other form of high-resolution
purification cannot differentiate between 2- and 3-series PGs (and other
non-PG components), they expressed their results as `ng immunoreactive PGE'
rather than ng PGE2. Others, however, have taken it for granted
that the product identified and quantified by EIA or RIA is only that defined
by the assay (e.g. Hagar et al.,
1989
; Martínez et al.,
1999
; Tahara and Yano,
2003
), despite the possibility of the presence of alternative
fatty acid substrates in these animals. It must be remembered that the
specificity of these assays totally depends on the antibodies used as well as
the degree to which samples have been extracted prior to the assay. Most of
the antibodies employed show low reactivity with other classical PGs so that
in defined cell types/tissues in mammals this approach presents few problems.
However, in invertebrates with the potential for novel PGs that have not been
screened for cross-reactivity with the antibodies, such an approach has clear
limitations. An additional problem arises because many aquatic invertebrates,
unlike terrestrial mammals, have significant amounts of arachidonic and
eicosapentaenoic acids in their phospholipids
(Stanley, 2000
). Both of these
can act as substrates for PG generation and EIA and RIA do not differentiate
between the products formed. For instance, both PGE2, formed from
arachidonate, and PGE3, derived from eicosapentaenoate, react
equally with the antibodies in some commercial PGE2 EIA kits. As
discussed by Taylor and Wellings
(1994
), unless full structural
analysis is achieved, there is little point in blindly using quantitative
approaches, such as EIA, that lack specificity. Essentially, confidence in the
accuracy of the identification and the quantification can only be achieved by
a combination of approaches such as solid phase extraction prior to separation
of analytes by high performance liquid chromatography (HPLC) or TLC, followed
by mass spectrometry or nuclear magnetic resonance (NMR) spectroscopy to
provide full structural identification and an appreciation of the
stereochemistry of the products. In very few cases has such an approach been
employed in the studies reported in Table
1 and therefore the results reported are equivocal.
Several authors have reported the presence of `PG-like' compounds in some
invertebrates. For example, in the blue mussel Mytilus edulis the
products of incubating gill, mantle or muscle with [14C]arachidonic
acid included one or more PG-like compounds that had an rf value on
TLC similar to authentic PGE2, PGF2 and
PGD2 (Srivastava and Mustafa
1985
). Aspirin and indomethacin inhibited the generation of
radiolabelled material, suggesting that they are products of COX activity.
Overall, however, there was no convincing evidence that the compounds formed
were identical to classical PGs. Similarly, leeches (Hirudo
medicinalis) are said to produce a PGI2-like substance
(Nikonov et al., 1999
).
Although the active substance inhibits human platelet aggregation and reacts
with antiserum to 6-keto-PGF1
, the stable breakdown product
of PGI2, no structural data were provided. It is entirely possible
that the active factor is a PG, but not necessarily PGI2. In the
snail Lymnaea stagnalis, the principal prostanoid synthesized
following incubation of various tissues with radiolabelled arachidonate, did
not correspond chromatographically to any authentic classical PG and was hence
termed `PG-like' (Clare et al.,
1986
). The COX inhibitor, aspirin, at 10 mmol l-1
reduced but did not completely eliminate the generation of this putative
PG.
Finally, there are examples of studies with some invertebrates where
authors have used known classical PGs and other eicosanoids in bioassays
without first screening by any analytical method to see if the compound of
interest is synthesised in the animal studied. Such an approach often results
in the finding of biological activity without any indication that the animal
or tissue under study can synthesize the appropriate substance. An example of
this comes from work with sand dollars (Echinaracnius parma) where
leukotriene B4 (LTB4), a 5-lipoxygenase product, has
been found to regulate intracellular Ca2+ levels in eggs
(Silver et al., 1994) when
studies with eggs from other echinoderms (sea urchins, Stronglyocentrotus
purpuratus) have shown categorically that the lipoxygenase products
generated did not include LTB4
(Hawkins and Brash, 1987
).
Hence the natural eicosanoid that regulates calcium changes in echinoderm eggs
is highly unlikely to be LTB4.
![]() |
Recent insights from studies on barnacles |
---|
|
The second stage that may be influenced by eicosanoids is settlement when
the cyprid larvae attach to the substratum, prior to a radical metamorphosis
that ultimately gives rise to sessile adults
(Fig. 3). Knight et al.
(2000) demonstrated in
Balanus amphitrite that PGE2, PGE3 and the
stable synthetic analogue of PGE2, 15,15-dimethyl-PGE2,
caused a dose-dependent inhibition of larval settlement, while indomethacin, a
COX inhibitor, stimulated this process. They concluded from these preliminary
findings that PGs might play key roles in controlling larval settlement.
Studies using EIA alone found that the soft tissues of B. amphitrite
generate significant amounts of PGE immunoreactive material
(Knight et al., 2000
), but
taking into account the problems of using EIA alone for PG identification
already discussed, such preliminary results required confirmation. Therefore,
the potential biosynthesis of PGs by adult and larval barnacles was studied
using a combination of solid phase extraction of analytes, separation by
reverse phase-HPLC, followed by mass spectrometry (MS) of fractions found to
have immunoreactivity in EIA. Such an approach was chosen to categorically
identify all potential PGs generated. HPLC-negative ion electrospray MS of
calcium ionophore-challenged barnacle tissues revealed two major peaks with
PG-like masses and elution times. Firstly, a component with a retention time
of
14.23 min eluting
0.7 min earlier than the authentic
PGF3
, which generated a deprotonated (M-H-) ion
at an m/z 353, and secondly, a component that eluted at
16.43
min between authentic standards PGF2
and PGE2
(equivalent to peaks I and II, respectively, in
Fig. 4), generating an
M-H- at m/z 351. In order to boost product generation and
overcome the problems of low sensitivity (ng levels) on HPLC-MS, B.
amphitrite tissue samples were pre-incubated with the exogenous fatty
acids EPA and AA. This generated two additional peaks with PG-like masses, an
m/z 353 species with a retention time of
18.54 min and an
m/z 351 species, which eluted at
20.66 min (peaks III and IV,
respectively, in Fig. 4). However, when samples were pre-incubated with the COX inhibitor indomethacin
(25 µmol l-1), all four peaks remained, suggesting that the peak
identities were either non-prostanoid or that they were prostanoids derived
via a non-COX route. HPLC fractions containing PG-like material were
derivatised for electron impact GC-MS. This revealed the peak identities to be
the lipoxygenase products, trioxilin A4 (peak II,
Fig. 4) and trioxilin
A3 (peak III, Fig.
4). The two remaining PG-like peaks (I and IV,
Fig. 4) could not be identified
on electron impact GC-MS. Thus, the presence of any classical prostanoids in
B. amphitrite including PGE2/3, PGF2/3
,
PGD2/3, TxA2/3, PGI2/3 as well as
PGA2/3 and PGJ2/3 could not be confirmed on either
HPLC-MS or GC-MS. Hence it was concluded that they are either not produced or
they are present in levels below the detection limit (ng) on HPLC/GC-MS. The
latter hypothesis was further supported by the repeated detection of >100
pg mg-1 protein of PG immunoreactivity on total PG, PGE and PGF EIA
kits predominantly in HPLC fractions between 14-18 min, but particularly in
the 16-17 min time fraction e.g. (Fig.
4). When samples were prepared in the presence of indomethacin (a
COX inhibitor), immunoreactivity was completely suppressed, suggesting that
this material was probably derived through a COX route (i.e. PG-like) and was
not the result of antibody cross reactivity with trioxilin A4 or
other lipoxygenase-derived products.
|
Overall these barnacle studies highlight the fact that it is extremely easy to mis-identify other compounds (e.g. trioxilins) as PG-like compounds if no electron impact GC-MS work is conducted. It also indicates the problems encountered in gaining structural elucidation when material is generated in extremely low levels (i.e. sub-ng), as appears to be the case in B. amphitrite.
![]() |
Prostanoid biosynthetic pathways in invertebrates |
---|
Not only has the existence of COX been shown in some corals but also
potential mechanisms for the biosynthesis of the unusual PG esters have been
proposed (Valmsen et al.,
2001). In this, the action of COX on arachidonate leads to the
generation of an unstable PG endoperoxide similar to PGH2 found in
mammals but with the R rather than the S configuration at
C15 (Fig. 5). Following this
COX-mediated stage, the 15(R)-PGE2 formed is converted to
its methyl ester and acetylated to give rise ultimately to the large amounts
of stable 15R-PGA2-methyl ester and
15R-acetate-PGA2-methyl ester stored in these animals.
|
Recent findings by Brash and colleagues on lipoxygenases in P.
homomalla may explain how clavulones and related cyclopentenone
eicosanoids are formed (Boutaud and Brash,
1999; Tijet and Brash,
2002
). This coral contains an unusual allene oxide synthase -
lipoxygenase fusion protein. Tijet and Brash
(2002
) have suggested that
clavulones are formed by a pathway that commences with the action of
8(R)lipoxygenase on arachidonic acid to give rise to 8R
hydroperoxyeicosatetraenoic acid that is subsequently converted to allene
oxide by the allene oxide synthase activity. Subsequently, this gives rise to
clavulones by a method analogous to that employed in plants in the formation
of jasmonic acid from linolenic acid
(Tijet and Brash, 2002
). This
provides a much needed explanation of how clavulones and related forms may be
synthesized in marine invertebrates.
Little is known of the presence of any of the other enzymes involved in the
generation of classical PGs in invertebrates with the exception of PGD
synthase in parasites. Since the discovery of Fusco et al.
(1985) that the penetration of
the human host by cercariae of Schistosoma mansoni is apparently
influenced by PGs, there has been heightened interest in the possibility that
both protozoan and metazoan parasites may improve their success of survival
either by generation of PGs themselves or by modifying the host's ability to
generate PGs. Haemopoietic PGD synthase is a member of the sigma-class
glutathione S-transferase (GST) family
(Kanaoka et al., 2000
). GSTs
in general are multifunctional enzymes found in both invertebrates and
vertebrates, and it is unlikely that all of the sigma-class forms will have PG
synthase activity because some lack the amino acid residues involved in
substrate (PGH2) binding
(Thomson et al., 1998
).
Recently, however, both the sigma class GSTs from the filarial parasite
Onchocerca volvulus (Sommer et
al., 2003
) and Schistosoma
(Johnson et al., 2003
) have
been shown to convert PGH2 to PGD2, while in
Ascaridia galli a purified GST has PGE synthase activity
(Meyer et al., 1996
). In the
case of the O. volvulus GST (Ov-GST-1), this enzyme is
located at the margins of the parasite, in the cuticle and hence in a prime
location to influence the host responses. Similarly, in Brugia malayi
and Wuchereria bancrofti, the parasite microfilariae become coated in
PGE2 following in vitro culture as a result of its
generation in the parasites (Liu et al.,
1992
). As PGs have been shown to be involved in immune regulation
in mammals and some other vertebrates (e.g.
Garrone et al., 1994
;
Knight and Rowley, 1995
) as
well as in inflammation (Colville-Nash and
Gilroy, 2000
), the synthesis of these compounds by parasites could
affect the host immune response favouring parasite survival and host
penetration (Daugschies and Joachim,
2000
; Noverr et al.,
2003
).
![]() |
Insights from the Ciona genome |
---|
![]() |
Concluding remarks |
---|
![]() |
List of abbreviations |
---|
![]() |
Acknowledgments |
---|
![]() |
Footnotes |
---|
![]() |
References |
---|
Agnisola, C., Venzi, R., Mustafa, T. and Tota, B. (1994). The systemic heart of Octopus vulgaris: effects of exogenous arachidonic acid and capability of arachidonate metabolism. Mar. Biol. 120,47 -53.
Aljamali, M., Bowman, A, S., Dillwith, J, W., Tucker, J, S., Yates, G, W., Essenberg, R. C. and Sauer, J. R. (2002). Identity and synthesis of prostaglandins in the lone star tick, Amblyomma americanum (L.), as assessed by radio-immunoassay and gas chromatography/mass spectrometry. Insect Biochem. Mol. Biol. 32,331 -341.[CrossRef][Medline]
Baker, B. J. and Scheuer, P. J. (1994). The punaglandins: 10-chloroprostanoids from the octocoral Telesto riisei. J. Nat. Prod. 57,1346 -1353.[Medline]
Baker, B. J., Okuda, R. K., Yu, P. T. K. and Scheuer, P. J. (1985). Punaglandins: halogenated antitumor eicosanoids from the octocoral Telesto riisei. J. Am. Chem. Soc. 107,2976 -2977.
Bao, Y., Pucci, M. L., Chan, B. S., Lu, R., Ito, S. and Schuster, V. L. (2001). Prostaglandin transporter PGT is expressed in cell types that synthesize and release prostanoids. Am. J. Physiol. 282,F1103 -F1110.
Boutaud, O. and Brash, A. R. (1999).
Purification and catalytic activities of the two domains of the allene oxide
synthase-lipoxygenase fusion protein of the coral Plexaura homomalla.
J. Biol. Chem. 274,33764
-33770.
Bowman, A. S., Dillwith, J. W. and Sauer, J. R. (1996). Tick salivary prostaglandins: presence, origin and significance. Parasitol. Today 12,388 -396.[CrossRef][Medline]
Casapullo, A., Scognamiglio, G. and Cimino, G. (1997). Mucosin: a new bicyclic eicosanoid from the Mediterranean sponge Reniera mucosa. Tetrahedon Lett. 38,3643 -3646.[CrossRef]
Chandrasekharan, N. V., Dai, H., Roos, L. T., Evanson, N. K.,
Tomsik, J., Elton, T. S and Simmons, D. L. (2002). COX-3, a
cyclooxygenase-1 variant inhibited by acetaminophen and other
analgesic/antipyretic drugs: Cloning, structure, and expression.
Proc. Natl. Acad. Sci. USA
99,13926
-13931.
Christ, E. J. and van Dorp. D. A. (1972). Comparative aspects of prostaglandin biosynthesis in animal tissues. Biochim. Biophys. Acta 270,537 -545.
Cimino, G., Spinella, A. and Sodano, G. (1989). Naturally occurring prostaglandin-1,15-lactones. Tetrahedron. Lett. 30,3589 -3592.[CrossRef]
Cimino, G., Crispino, A., Di Marzo, V., Sodano, G., Spinella, A. and Villani, G. (1991a). A marine mollusc provides the first example of in vivo storage of prostaglandins: Prostaglandin-1,15-lactones. Experientia 47, 56-60.[Medline]
Cimino, G., Crispino, A., Di Marzo, V., Spinella, A. and Sodano, G. (1991b). Prostaglandin 1,15-lactones of the F series from the nudibranch mollusc Tethys fimbria. J. Org. Chem. 56,2907 -2911.
Clare, A. S., Walker, G., Holland, D. L. and Crisp, D. J. (1982). Barnacle egg hatching: a novel role for a prostaglandin-like compound. Mar. Biol. Lett. 3, 113-120.
Clare, A. S., van Elk, R. and Feyen, J. H. M. (1986). Eicosanoids: their biosynthesis in accessory sex organs of Lymnaea stagnalis (L.). Int. J. Invert. Reprod. Dev. 10,125 -131.
Colville-Nash, P. R. and Gilroy, D. W. (2000). COX-2 and the cyclopentenone prostaglandins - a new chapter in the book of inflammation? Prost. Lipid Mediat. 62, 33-43.[CrossRef]
Cooper, E. L. and Parrinello, N. (2001). Immunodefense in tunicates: cells and molecules. In The Biology of Ascidians (ed. H. Sawada, H. Yokosawa and C. C. Lambert), pp.383 -394. Tokyo: Springer-Verlag.
Corey, E. J., D'Alarcao, M., Matsuda, S., Lansbury, P. T., Jr. and Yamada, Y. (1987). Intermediacy of 8-(R)-HPETE in the conversion of arachidonic acid to pre-clavulone a by Clavularia viridis. Implications for the biosynthesis of marine prostanoids. J. Am. Chem. Soc. 109,289 -290.
Daugschies, A. and Joachim, A. (2000). Eicosanoids in parasites and parasitic infections. In Advances in Parasitology, vol. 46 (ed. J. R. Baker, R. Muller and D. Rollinson), pp. 181-240. London: Academic Press.[Medline]
Dehal, P. et al. (2002). The draft genome of
Ciona intestinalis: insights into chordate and vertebrate origins.
Science 298,2157
-2167.
Di Marzo, V., Cimino, G., Crispino, A., Minardi, C., Sodano, G. and Spinella, A. (1991). A novel multifunctional metabolic pathway in a marine mollusc leads to unprecedented prostaglandin derivatives (prostaglandin 1,15-lactones). Biochem. J. 273,593 -600.[Medline]
DuBois, R. N., Abramson, S. B., Crofford, L., Gupta, R. A.,
Simon, L. S., Van de Putte, L. B. A. and Lipsky, P. E.
(1998). Cyclooxygenase in biology and disease. FASEB
J. 12,1063
-1073.
Frolich, J. C. and Stichtenoth, D. O. (1998). Renal side effects of NSAIDs: role of COX-1 and COX-2. In Selective COX-2 Inhibitors: Pharmacology, Clinical Effects and Therapeutic Potential (ed. J. Vane and J. Botting), pp.87 -98. Dordrecht: Kluwer Academic Publishers.
Fusco, A. C., Salafsky, B. and Kevin, M. B. (1985). Schistosoma mansoni: Eicosanoid production by cercariae. Exp. Parasitol. 59, 44-50.[Medline]
Fusco, A. C., Salafsky, B. and Delbrook, K. (1986). Schistosoma mansoni: production of cercarial eicosanoids as correlates of penetration and transformation. J. Parasitol. 72,397 -404.[Medline]
Fusco, A. C., Salafsky, B. and Shibuya, T. (1993). Cytokine and eicosanoid regulation by Schistosoma mansoni during LSE penetration. Med. Inflamm. 2, 73-77.
Garavito, R. M. and DeWitt, D. L. (1999). The cyclooxygenase isoforms: structural insights into the conversion of arachidonic acid to prostaglandins. Biochim. Biophys. Acta 1441,278 -287.[Medline]
Garrone, P., Galibert, L., Rousset, F., Fu, S. H. and
Banchereau, J. (1994). Regulatory effects of prostaglandin
E2 on the growth and differentiation of human B lymphocytes
activated through their CD40 antigen. J. Immunol.
152,4282
-4290.
Gerhart, D. J. (1986). Prostaglandin A2 in the Caribbean gorgonian Plexaura homomalla: Evidence against allelopathic and antifouling roles. Biochem. System. Ecol. 4,417 -421.
Gerhart, D. J. (1991). Emesis, learned aversion, and the chemical defense in octocorals: a central role for prostaglandins? Am. J. Physiol. 260,R839 -R843.[Medline]
Gierse, J. K., McDonald, J. J., Hauser, S. D., Rangwala, C. M.,
Koboldt, C. M. and Seibert, K. (1996). A single amino acid
difference between cyclooxygenase-1 (COX-1) and -2 (COX-2) reverses the
selectivity of COX-2 specific inhibitors. J. Biol.
Chem. 271,15810
-15814.
Groweiss, A. and Fenical, W. (1990).
PGF2-9-0-acetate methyl ester, a minor naturally occurring
prostaglandin from the gorgonian coral Plexaura homomalla.
J. Nat. Prod. 53,222
-223.
Hagar, A. F., Hwang, D. H. and Dietz, T. H. (1989). Lipoxygenase activity in the gills of the freshwater mussel, Ligumia subrostrata. Biochim. Biophys. Acta 1005,162 -169.
Halushka, P. V. (2000). Thromboxane A(2) receptors: where have you gone? Prost. Lipid Mediat. 60,175 -189.[CrossRef]
Hampson, A. J., Rowley, A. F., Barrow, S. E. and Steadman, R. (1992). Biosynthesis of eicosanoids by blood cells of the crab, Carcinus maenas. Biochim. Biophys. Acta 1124,143 -150.[Medline]
Hara, S., Miyata, A., Yokoyama, C., Inoue, H., Brugger, R.,
Lottspeich, F., Ullrich, V. and Tanabe, T. (1994). Isolation
and molecular cloning of prostacyclin synthase from bovine endothelial cells.
J. Biol. Chem. 269,19897
-19903.
Hawkey, C. J. (1999). COX-2 inhibitors. The Lancet 353,307 -314.[CrossRef][Medline]
Hawkins, D. J. and Brash, A. R. (1987). Eggs of
the sea urchin, Strongylocentrotus purpuratus, contain a prominent
(11R) and (12R) lipoxygenase activity. J. Biol. Chem.
262,7629
-7634.
Hayaishi, O. (2000). Molecular mechanisms of sleep-wake regulation: a role of prostaglandin D2. Phil. Trans. R. Soc. Lond. 355,275 -280.[CrossRef][Medline]
Hayaishi, O., Matsumura, H., Onoe, H., Koyama, Y. and Watanabe, Y. (1990). Sleep-wake regulation by PGD2 and E2. In Advances in Prostaglandin, Thromboxane and Leukotriene Research 21 (ed. B. Samuelsson, P. W. Ramwell, R. Paoletti, G. Folco and E. Granström), pp.723 -726. Raven Press: New York.
Hill, E. M., Holland, D. L. and East, J. (1993). Egg hatching activity of trihydroxyated eicosanoids in the barnacle Balanus balanoides. Biochim. Biophys. Acta 1157,297 -303.[Medline]
Hirata, Y., Hayashi, H., Ito, S., Kikawa, Y., Ishibashi, M.,
Sudo, M., Miyazaki, H., Fukushima, M., Narumiya, S. and Hayaishi, O.
(1988). Occurrence of 9-deoxy-9,
12-13. 14-dihydroprostaglandin D2 in human urine.
J. Biol. Chem. 263,16619
-16625.
Honda, A., Mori, Y., Iguchi, K. and Yamada, Y. (1988). Structure requirements for antiproliferative and cytotoxic activities of marine coral prostanoids from the Japanese stolonifer Clavularia viridis against human myeloid leukemia cells in culture. Prostaglandins 36,621 -630.[CrossRef][Medline]
Iguchi, K., Kaneta, S., Mori, K., Yamada, Y. (1985). Chlorovulones, new halogenated marine prostanoids with an antitumor activity from the stolonifer Clavularia viridis Quoy and Gaimard. Tetrahedron Lett. 26,5787 -5790.[CrossRef]
Iguchi, K., Kaneta, S., Mori, K., Yamada, Y., Honda, A. and Mori, Y. (1986). Bromovulone 1 and Ioduvulone 1, unprecedented brominated and iodinated marine prostanoids with antitumour activity isolated from the Japanese stolonifer Clavularia viridis Quoy and Gaimard. J. Chem. Soc. Chem. Commun. 1986,981 -982.[CrossRef]
Iwashima, M., Okamoto, K. and Iguchi, K. (1999). Clavirins, a new type of marine oxylipins with growth-inhibitory activity from the Okinawan soft coral, Clavularia viridis. Tetrahedron Lett. 40,6455 -6459.[CrossRef]
Jeffery, W. R. (2002). Ascidian gene-expression profiles. Genome Biol. 3,1030 .1-1030.4.
Johnson, K. A., Angelucci, F., Bellelli, A., Hervé, M., Fontaine, J., Tsernoglou, D., Capron, A., Trottein, F. and Brunori, M. (2003). Crystal structure of the 28 kDa glutathione S-transferase from Schistosoma haematobium. Biochemistry 42,10084 -10094.[CrossRef][Medline]
Johnson, M. H. and Everitt, B. J. (2000). Essential Reproduction (5th edn.). Oxford: Blackwell Science.
Kanai, N., Lu, R., Satriano, J. A., Bao, Y., Wolkoff, A. W. and Schuster, V. L. (1995). Identification and characterization of a prostaglandin transporter. Science 268,866 -869.[Medline]
Kanaoka, Y., Fujimori, K., Kikuno, R., Sakaguchi, Y., Urade, Y.
and Hayaishi, O. (2000). Structure and chromosomal
localization of human and mouse genes for hematopoietic prostaglandin D
synthase. Eur. J. Biochem.
267,3315
-3322.
Kikuchi, H., Tsukitani, Y., Iguchi, K. and Yamada, Y. (1982). Clavulones, new type of prostanoids from the stolonifer Clavularia viridis Quoy and Gaimard. Tetrahedron Lett. 23,5171 .[CrossRef]
Knight, J. and Rowley, A. F. (1995). Immunoregulatory activities of eicosanoids in the rainbow trout (Oncorhynchus mykiss). Immunol. 85,389 -393.[Medline]
Knight, J., Taylor, G. W., Wright, P., Clare, A. S. and Rowley, A. F. (1999). Eicosanoid biosynthesis in an advanced deuterostomate invertebrate, the sea squirt (Ciona intestinalis). Biochim. Biophys. Acta 1436,467 -478.[Medline]
Knight, J., Rowley, A. F., Yamazaki, M. and Clare, A. S. (2000). Eicosanoids are modulators of larval settlement in the barnacle, Balanus amphitrite. J. Mar. Biol. Assn UK 80,113 -117.
Koljak, R., Järving, I., Kurg, R., Boeglin, W. E., Varvas,
K., Valmsen, K., Ustav, M., Brash, A. R. and Samel, N.
(2001). The basis of prostaglandin synthesis in coral.
J. Biol. Chem. 276,7033
-7040.
Liu, L. X., Serhan, C. N. and Weller, P. F. (1990). Intravascular filarial parasites elaborate cyclooxygenase-derived eicosanoids. J. Exp. Med. 172,993 -996.[Abstract]
Liu, L. X., Buhlmann, J. E. and Weller, P. F. (1992). Release of prostaglandin E2 by microfilariae of Wuchereria bancrofti and Brugia malayi. Am. J. Trop. Med. Hyg. 46,520 -523.[Medline]
Mancini, J. A., Blood, K., Guay, J., Gordon, R., Claveau, D.,
Chan, C.-C. and Riendeau, D. (2001). Cloning, expression, and
up-regulation of inducible rat prostaglandin E synthase during
lipopolysaccharide-induced pyresis and adjuvant-induced arthritis.
J. Biol. Chem. 276,4469
-4475.
Martínez, G., Mettifogo, L., Lenoir, R. and Campos, E. O. (1999). Prostaglandins and reproduction of the scallop Argopecten purpuratus: I. Relationship with gamete development. J. Exp. Zool. 284,224 -231.
Meyer, D. J., Muimo, R., Thomas, M., Coates, D. and Isaac, R. E. (1996). Purification and characterization of prostaglandin-H E-isomerase, a sigma-class glutathione S-transferase, from Ascaridia galli. Biochem. J. 313,223 -227.[Medline]
Moncada, S. and Vane, J. R. (1979). Arachidonic acid metabolites and the interactions between platelets and blood-vessel walls. N. Engl. J. Med. 300,1142 -1147.[Medline]
Murakami, M., Nakatani, Y., Tanioka, T. and Kudo, I. (2002). Prostaglandin E synthase. Prost. Lipid Mediat. 68-69,383 -399.[CrossRef]
Murakami, M., Nakashima, K., Kamei, D., Masuda, S., Ishikawa,
Y., Ishii, T., Ohmiya, Y., Watanabe, K. and Kudo, I. (2003).
Cellular prostaglandin E2 production by membrane-bound
prostaglandin E synthase-2 via both cyclooxygenases-1 and -2. J.
Biol. Chem. 278,37937
-37947.
Negishi, M. and Katoh, H. (2002). Cyclopentenone prostaglandin receptors. Prost. Lipid Mediat. 68-69,611 -617.[CrossRef]
Nikonov, G. I., Titova, E. A. and Seleznev, K. G. (1999). A stable prostacyclin-like substance produced by the medicinal leech Hirudo medicinalis. Prost. Lipid Mediat. 58,1 -7.[CrossRef]
Noverr, M. C., Erb-Downward, J. R. and Huffnagle, G. B. (2003). Production of eicosanoids and other oxylipins by pathogenic eukaryotic microbes. Curr. Microbiol. Rev. 16, 517.[CrossRef]
Osada, M., Nishikawa, M. and Nomura, T. (1989). Involvement of prostaglandins in the spawning of the scallop, Patinopecten yessoensis. Comp. Biochem. Physiol. 94,595 -601.[CrossRef]
Pawlik, J. R. and Fenical, W. (1989). A re-evaluation of the ichthyodeterrent role of prostaglandins in the Caribbean gorgonian coral Plexaura homomalla. Mar. Ecol. Prog. Ser. 52,95 -98.
Pedibhotla, V. K., Sauer, J. R. and Stanley-Samuelson, D. W. (1997). Prostaglandin biosynthesis by salivary glands isolated from the lone star tick, Amblyomma americanum. Insect Biochem. Mol. Biol. 27,255 -261.[CrossRef][Medline]
Pope, E. and Rowley, A. F. (2002). The heart of
Ciona intestinalis: eicosanoid-generating capacity and the effects of
precursor fatty acids and eicosanoids on heart rate. J. Exp.
Biol. 205,1577
-1583.
Pucci, M. L., Bao, Y., Chan, B., Itoh, S., Lu, R., Copeland, N. G., Gilbert, D. J., Jenkins, N. A. and Schuster, V. L. (1999). Cloning of mouse prostaglandin transporter PGT cDNA: species-specific substrate affinities. Am. J. Physiol. 277,R734 -R741.[Medline]
Reddy, S. T. and Herschman, H. R. (1997). Prostaglandin synthase-1 and prostaglandin synthase-2 are coupled to distinct phospholipases for the generation of prostaglandin D2 in activated mast cells. J. Biol. Chem. 72,3231 -3237.[CrossRef]
ezanka, T. and Dembitsky, V. M. (2003).
Brominated oxylipins and oxylipin glycosides from red sea corals.
Eur. J. Org. Chem. 2003,309
-316.[CrossRef]
Roberts, S. B., Langenau, D. M. and Goetz, F. W. (2000). Cloning and characterization of prostaglandin endoperoxide synthase-1 and -2 from the brook trout ovary. Mol. Cell Endocrinol. 160,89 -97.[CrossRef][Medline]
Rowley, A. F., Hill, D. J., Ray, C. E. and Munro, R. (1997). Haemostasis in fish - an evolutionary perspective. Thromb. Haemostasis 77,227 -233.[Medline]
Saintsing, D. G., Hwang, D. H. and Dietz, T. H.
(1983). Production of prostaglandins E2 and
F2 in the freshwater mussel Ligumia subrostrata:
Relation to sodium transport. J. Pharm. Exp. Ther.
226,455
-461.[Abstract]
Shida, K., Terajima, D., Uchino, R., Ikawa, S., Ikeda, M., Asano, K., Watanabe, T., Azumi, K., Nonaka, M., Satou, Y. et al. (2003). Hemocytes of Ciona intestinalis express multiple genes involved in innate immune host defense. Biochem. Biophys. Res. Comm. 302,207 -218.[CrossRef][Medline]
Silver, R. B., Oblak, J. B., Jeun, G. S., Sung, J. J. and Dutta,
T. C. (1994). Leukotriene B4, an arachidonic acid
metabolite, regulates intracellular calcium release in eggs and mitotic cells
in the sand dollar (Echinaracnius parma). Biol.
Bull. 187,242
-244.
Sommer, A., Rickert, R., Fischer, P., Steinhart, H., Walter, R.
D. and Liebau, E. (2003). A dominant role for extracellular
glutathione S-transferase from Onchocerca volvulus is the production
of prostaglandin D2. Infect. Immun.
71,3603
-3606.
Song, W.-C. and Brash, A. R. (1991). Investigation of the allene oxide pathway in the coral Plexaura homomalla: formation of novel ketols and isomers of prostaglandin A2 from 15-hydroxyeicosatetraenoic acid. Archiv. Biochem. Biophys. 290,427 -435.[CrossRef][Medline]
Spaziani, E. P., Hinsch, G. W. and Edwards, S. C.
(1993). Changes in prostaglandin E2 and
F2 during vitellogenesis in the Florida crayfish
Procambarus paeninsulanus. J. Comp. Physiol.
163,541
-549.
Spaziani, E. P., Hinsch, G. W. and Edwards, S. C.
(1995). The effect of prostaglandin E2 and
prostaglandin F2 on ovarian tissue in the Florida crayfish
Procambarus paeninsulanus. Prostaglandins
50,189
-200.[Medline]
Srivastava, K. C. and Mustafa, T. (1985). Formation of prostaglandins and other comparable products during aerobic and anaerobic metabolism of [1- 14C]arachidonic acid in the tissues of sea mussels, Mytilus edulis L. Mol. Physiol. 8, 101-112.
Stanley, D. W. (2000). Eicosanoids in Invertebrate Signal Transduction Systems. Princeton: Princeton University Press.
Stanley-Samuelson, D. W. (1991). Comparative eicosanoid physiology in invertebrate animals. Am. J. Physiol. 260,R849 -R853.[Medline]
Stanley, D. W. and Miller, J. S. (1998). Eicosanoids in animal reproduction: what can we learn from invertebrates? In Eicosanoids and Related Compounds in Plants and Animals (ed. A. F. Rowley, H. Kühn and T. Schewe), pp.183 -196. London: Portland Press.
Tahara, D. and Yano, I. (2003). Development of hemolymph prostaglandins assay systems and their concentration variations during ovarian maturation in the kuruma prawn, Penaeus japonicus. Aquaculture 220,791 -800.[CrossRef]
Taylor, G. W. and Wellings, R. (1994). Measurement of fatty acids and their metabolites. In The Handbook of Immunopharmacology: Lipid Mediators (ed. F. M. Cunningham), pp. 33-59. London: Academic Press.
Thomson, A. M., Meyer, D. J. and Hayes, J. D. (1998). Sequence, catalytic properties and expression of chicken glutathione dependent prostaglandin D2 synthase, a novel class sigma glutathione S-transferase. Biochem. J. 333,317 -325.[Medline]
Tijet, N. and Brash, A. R. (2002). Allene oxide synthases and allene oxides. Prost. Lipid Mediat. 68-69,423 -431.[CrossRef]
Tsuboi, K., Sugimoto, Y. and Ichikawa, A. (2002). Prostanoid receptor subtypes. Prost. Lipid Mediat. 68-69,535 -556.[CrossRef]
Ujihara, M., Tsuchida, S., Satoh, K., Sato, K. and Urade, Y.
(1988). Biochemical and immunological demonstration of
prostaglandin D2, E2, and F2 formation
from prostaglandin H2 by various rat glutathione S-transferase
isozymes. Arch. Biochem. Biophys.
264, 428.[Medline]
Ullrich, V., Zou, M. H. and Bachschmid, M. (2001). New physiological and pathophysiological aspects on the thromboxane A2-prostacyclin regulatory system. Biochim. Biophys. Acta 1532,1 -14.[Medline]
Umatsu, S., Matsumoto, M., Takeda, K. and Akira, S.
(2002). Lipopolysaccharide-dependent prostaglandin E2
production is regulated by the glutathione-dependent prostaglandin
E2 synthase gene induced by Toll-like receptor 4/Myd88/NF-IL-6
pathway. J. Immunol.
168,5811
-5816.
Urade, Y. and Eguchi, N. (2002). Lipocalin-type and hematopoietic prostaglandin D synthases as a novel example of functional convergence. Prost. Lipid Mediat. 68-69,375 -382.[CrossRef]
Valmsen, K., Järving, I., Boeglin, W. E., Varvas, K.,
Koljak, R., Pehk, T., Brash, A. R. and Semel, N. (2001). The
origin of 15R-prostaglandins in the Caribbean coral Plexaura
homomalla: Molecular cloning and expression of a novel cyclooxygenase.
Proc. Natl. Acad. Sci. USA
98,7700
-7705.
Varvas, K., Järving, I., Koljak, R., Vahemets, A., Pehk,
T., Müürisepp, A.-M. and Lille, Ü. (1993). In
vitro biosynthesis of prostaglandins in the White Sea soft coral Gersemia
fruticosa: Formation of optically active PGD2,
PGE2, PGF2 and 15-keto-PGF2
from arachidonic acid. Tetrahedron Lett.
34,3643
-3646.[CrossRef]
Varvas, K., Järving, I., Koljak, R., Valmsen, K., Brash, A.
R. and Samel, N. (1999). Evidence of a cyclooxygenase-related
prostaglandin synthesis in coral. J. Biol. Chem.
274,9923
-9929.
Vogan, C. L., Maskrey, B. H., Taylor, G. W., Henry, S.,
Pace-Asciak, C. R., Clare, A. S. and Rowley, A. F. (2003).
Hepoxilins and trioxilins in barnacles: an analysis of their potential roles
in egg hatching and larval settlement. J. Exp. Biol.
206,3219
-3226.
Wang, L. and Kulmacz, R. J. (2002). Thromboxane synthase: structure and function of protein and gene. Prost. Lipid Mediat. 68-69,409 -422.[CrossRef]
Warner, T. D and Mitchell, J. A. (2002).
Cyclooxygenases-3 (COX-3): Filling in the gaps toward a COX continuum?
Proc. Natl. Acad. Sci. USA
99,13371
-13373.
Watanabe, K., Sekine, M., Takahashi, H. and Iguchi, K. (2001). New halogenated marine prostanoids with cytotoxic activity from the Okinawan soft coral Clavularia viridis. J. Nat. Prod. 64,1421 -1425.[CrossRef][Medline]
Weinheimer, A. J. and Spraggins, R. L. (1969). The occurrence of two new prostaglandin derivatives (15-epi-PGA2 and its acetate methyl ester) in the gorgonian Plexaura homomalla: chemistry of coelenterates XV. Tetrahedron Lett. 59,5185 -5188.[CrossRef][Medline]
Wright, D. H., Abran, D., Bhattacharya, M., Hou, X., Bernier, S. G., Bouayad, A., Fouron, J.-C., Vazquez-Tello, A., Beauchamp, M. H. et al. (2001). Prostanoid receptors: ontogeny and implication in vascular physiology. Am. J. Physiol. 281,R1343 -R1360.
Yang, T., Forrest, S. J., Stine, N., Endo, Y., Pasumarthy, A., Castrop, H., Aller, S., Forrest, J. N., Jr, Schnermann, J. and Briggs, J. (2002). Cyclooxygenase cloning in dogfish shark, Squalus acanthius, and its role in rectal gland C1 secretion. Am. J. Physiol. 283,R631 -R637.
Zou, J., Neumann, N. F., Holland, J. W., Belosevic, M., Cunningham, C., Secombes, C. J. and Rowley, A. F. (1999). Fish macrophages express a cyclo-oxygenase-2 homologue after activation. Biochem. J. 340,153 -159.[CrossRef][Medline]