Lung Membrane Transport Group, Department of Child Health, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY; and Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, United Kingdom
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Because G protein-regulated cation channels in
type II pneumocytes constitute the most likely pathway for alveolar
Na+ entry, we explored the
hypothesis that a G protein-coupled prostaglandin (PG)
E2 receptor controls perinatal
lung alveolar Na+ transport.
[3H]PGE2
binding to the alveolar apical membrane was trypsin sensitive and
showed a rank order of competitive inhibition:
PGE2 = PGE1 > PGD2 > PGF2. Kinetic analysis
demonstrated both high-affinity [dissociation constant
(KD) = 2.1 ± 0.7 nM; maximal binding
(Bmax) = 27 ± 7 fmol/mg
protein] and low-affinity
(KD = 28 ± 2 nM; Bmax = 265 ± 29 fmol/mg
protein) binding sites. Modulation of high-affinity GTPase activity
identified a similar potency order
(IC50 = 11 mM for
PGF2
vs. 10-50 µM for
other PGs), suggesting that the receptors are G protein coupled.
Finally, 1 µM PGE2
(
IC25) increased conductive
22Na+
uptake into membrane vesicles only in the presence of 100 µM intravesicular GTP. The
KD value for the
high-affinity binding site together with the rank order of PG effect on
ligand binding and G protein function places this PG receptor in the
EP3 subtype, whereas
Na+ uptake studies suggest that it
helps maintain perinatal lung Na+
homeostasis.
sodium channel; prostaglandin E2 ; sodium ion
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
EFFICIENT LUNG ALVEOLAR Na+-channel function is crucial to survival. Epithelial Na+-channel "knockout" mice die of severe respiratory distress within 48 h of birth, with autopsy evidence of massive lung fluid overload (12). In humans, life-threatening neonatal respiratory distress commonly associates with lung alveolar and interstitial edema (2), implicating an underlying dysfunction of extra- or intracellular mechanisms regulating lung alveolar Na+ transport around the time of birth. After the characterization of the hormonal control (1) of this amiloride-inhibitable Na+-absorptive response (24), it is now imperative to understand the cellular mechanisms that regulate this absorptive process in order to work toward the development of therapeutic strategies for the treatment of lung alveolar fluid overload in the neonate.
Working toward this objective, we have recently identified
low-conductance, amiloride-sensitive,
Na+-selective channels in the
freshly isolated mature end-gestation (term) fetal type II pneumocyte,
which we propose may facilitate this
Na+-driven fluid-absorptive role
(8, 18). These channels are upregulated by polyunsaturated fatty acids
and by the nonhydrolyzable GTP analog guanosine
5'-O-(3-thiotriphosphate)
(GTPS; see Ref. 8a), implicating control via a G protein-linked
pathway.
Although most available information supports the hypothesis that
prostaglandins (PGs) play an important role in the regulation of ion
transport in the first-trimester fetal lung by stimulating fluid
secretion (4, 15, 19, 32), their effect on the fetal lung in late
gestation has not been studied. However, evidence from the renal
collecting tubule (an
Na+-absorbing epithelium) would
suggest that PGE2 is a likely
candidate for control of alveolar fluid absorption. Using perfused,
microdissected rabbit renal collecting tubule and adjacent thick
ascending limb (containing cation channels electrophysiologically
similar to perinatal mammalian lung; see Ref. 17), Grantham and Orloff (10) demonstrated a dual role for
PGE2 in regulating
Na+-linked water absorption in the
collecting tubule and thick ascending limb: at low concentrations
(109 M),
PGE2 inhibited, whereas at
relatively higher concentrations (
10
7 M), it stimulated
the arginine vasopressin-mediated water-absorptive response. Higher
concentrations of PGE2
(
10
7 M) also caused
stimulation of adenylyl cyclase activity in both collecting tubule and
thick limb cells (28). Collating this and related information, Smith
(26) developed a unifying biochemical paradigm for the role of
PGE2 in renal fluid transport.
Although PG receptors have been identified in the airway (6, 13), their existence in lung alveoli (with different functional priorities such as surfactant secretion and Na+ absorption) has not been reported. We adopted the following stepwise strategy to test our hypothesis: 1) identification of putative PGE2-binding sites in the term fetal lung alveolar type II pneumocyte apical membrane by radioligand binding; 2) exploration of the PG effect on G protein function in this membrane (because PGs act via G proteins in other tissues; see Refs. 16 and 26); and, finally, 3) study of possible PGE2-mediated regulation of Na+ transport in the same preparation. High-affinity GTPase activity was measured as a marker of G protein function; this method of measurement and its usefulness in assessing tissue G protein turnover have been established already (20). The measurement of the rate of Na+ uptake into vesicles of type II pneumocyte apical membrane has been validated by our group as a marker of conductive Na+ transport (8); this method was utilized to study the possible effect of PGE2 on Na+ channels in the type II pneumocyte apical membrane.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Materials
[Methods
Isolation of type II pneumocyte apical membrane. Apical membrane was prepared from late-gestation (<3 days preterm) fetal guinea pig lung as previously described (8). Briefly, lung lobes were excised at 2nd/3rd generation bronchi, placed in ice-cold homogenization medium [250 mM sucrose and 10 mM triethanolamine (TRA), pH 7.6 with HCl, containing 200 µg deoxyribonuclease I, 2.6 mg aprotinin A, 1.0 mg leupeptin, 1.0 mg pepstatin A, and 17.5 mg 4-(2-aminoethyl)benzenesulfonyl fluoride per 100 ml of medium], and homogenized in a Waring blender followed by a Polytron emulsifier (5 min; 4°C for both). After this, differential centrifugation and Mg2+ precipitation (in 75 mM NaCl, 50 mM MgCl2, and 10 mM HEPES, pH 7.4 with NaOH) were employed to yield a membrane fraction that was enriched with the apical membrane marker alkaline phosphatase (Identification of putative PGE2-binding
sites.
A
[3H]PGE2
binding assay was performed to identify putative
PGE2 receptors in the above
preparation. The conditions of the assay have been described earlier
(7). Briefly, membrane (50 µg protein) was incubated at 23°C with
the indicated amounts of [3H]PGE2
(earlier experiments had established that optimum radiolabeled PG
binding was achieved at room temperature). Incubations were performed
in triplicate in buffer solution (250 mM mannitol, 10 mM TRA, and 2 mM
MgCl2, pH 7.6 with HCl) in a total
volume of 200 µl in the presence of 10 nM
[3H]PGE2.
Because <1% of
[3H]PGE2
bound to the membrane, the concentration of free ligand remained
essentially constant throughout the experimental period. Parallel
experiments were run using a 1,000-fold excess of unlabeled PGE2 (10 µM) in the above
incubation mixture to determine the nonspecific binding; this value was
subtracted from the total binding to calculate the specific binding. At
the end of the incubation, the mixture was vacuum filtered through
glass microfilters (Whatman GF/C) that had been presoaked in assay
buffer. Each assay tube and filter was washed with 10 ml of the buffer
at 4°C. The filters were then dried and suspended in scintillation
fluid for measurement of radioactivity. In initial experiments, the
time course of association in binding was studied by incubating
membrane (50 µg protein) with
[3H]PGE2
(10 nM) in the absence (total binding) and in the presence (nonspecific
binding) of 10 µM unlabeled
PGE2. Subsequently,
[3H]PGE2
was incubated with membranes at 23°C for 30 min. The maximum binding capacity (Bmax) and
dissociation constant
(KD) were
obtained by an iterative fitting protocol (method of least spaces)
using one- and two-site models (FigP; Biosoft, Cambridge, UK). Finally, the membrane was incubated with trypsin (5 µg or 53.5 N-benzoyl-L-arginine ethyl ester hydrolysing units/50 µg membrane in 200 µl buffer) as
above. After the incubation, membranes were washed, and
[3H]PGE2
binding activity was determined.
PGE2-mediated regulation of conductive
Na+ transport.
Apical membrane was revesiculated in the presence of G protein
substrate (100 µM GTP or GTPS), and after the imposition of an
outwardly directed Na+ gradient, 1 µM PGE2 was added to
extravesicular solution at the initiation of the transport assay as
indicated by the conditions of the experiment. The detailed
Na+ uptake experiment protocol has
been extensively described by our group (8). Briefly, passing
NaCl-loaded vesicles (125 mM) through 1-ml Dowex 50X8-100 columns
enabled an outwardly directed Na+
gradient to be imposed across the vesicular membrane by resuspension in
a low-concentration NaCl solution (125 µM). Such a gradient results
in a negative intravesicular diffusion potential being established in
those vesicles containing conductive
Na+ pathways (channels), which in
turn drives tracer
22Na+
uptake. Intra- and extravesicular
22Na+
were separated from each other by a further cation exchange step. Uptake was examined as an initial rate (at 2 min). Intravesicular 22Na+
content (uptake) was calculated as picomoles of
22Na+
per milligram of protein per minute. Data are presented as the ratio of
uptake in the "experimental" group (e.g., in the presence of PG)
to the uptake in the appropriate (vehicle) control.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Identification of Putative PGE2-Binding Sites
Binding of 10 nM [3H]PGE2 was time dependent and saturable, with equilibrium being attained within 30 min of incubation, which was the time point chosen for all subsequent equilibrium binding experiments (data not shown). Addition of a large excess of unlabeled PGE2 (1,000-fold) to the reaction mixture at the beginning of the incubation reduced the binding of [3H]PGE2 to the membrane to ~40% of the total (see Fig. 2A), indicating the competitive nature of [3H]PGE2 binding. The binding isotherm shown in Fig. 1A is well fitted by a two-site model with affinities (KD) of 2.11 ± 0.70 and 27.83 ± 1.99 nM and Bmax of 27.46 ± 6.89 and 265.44 ± 29.13 fmol/mg protein. Separate theoretical isotherms using these calculated parameters are also shown for information. Transformation of the data to yield a Scatchard plot (Fig. 1B) clearly shows the presence of two binding sites. Incubation of the lung apical membrane with trypsin (53.5 U/50 µg protein in 200 µl buffer) completely abolished specific [3H]PGE2 binding (data not shown). The specificity of [3H]PGE2 binding was investigated by adding increasing concentrations (0.001-2.5 µM) of unlabeled PGs E1, E2, D2, and F2
|
|
PG Effect on G Protein Function
The dose responses of PGE1, PGE2, PGD2, and PGF2
|
PGE2 Effect on Lung Membrane is G Protein Specific
Fatty acids at micromolar concentrations can alter the physical characteristics of membrane to exert a possibly nonspecific effect on membrane enzymes (30). Because PGE2 belongs to the oxygenated C20 fatty acid family, the extent of this effect was assessed by comparing possible PGE2 inhibition of ouabain-insensitive ATPases with inhibition of high-affinity GTPase activity produced by PGE2. PGE2 (1 µM) attenuated the GTPase activity by 32.0 ± 4.0% (n = 3) and the ouabain-insensitive ATPase activity by only 2.1 ± 0.2% (n = 3), indicating that the effect of PGs was specific to G protein GTPase activity.PGE2-Mediated Regulation of Na+ Transport
Figure 4 shows that extravesicular PGE2 (1 µM) or intravesicular GTP (100 µM) in isolation produced no significant change in the initial rate of 22Na+ uptake (n = 7). In combination, however, these concentrations of PGE2 and GTP significantly increased the initial rate of 22Na+ uptake 1.38 ± 0.09-fold above control (P < 0.05; n = 7), indicating that PGE2 stimulation of apical Na+ channels is G protein dependent. The differences between the effect of PGE2 and GTP in combination and that of PGE2 or GTP alone were also significant (P < 0.05; n = 7). There was no significant difference between the increase in the initial rate of 22Na+ uptake achieved with intravesicular GTP
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
This paper confirms the presence of a high-affinity PGE2-binding site on the type II pneumocyte apical membrane of the term guinea pig fetus. Kinetic analysis of [3H]PGE2 binding to type II pneumocyte apical membrane shows that this binding is saturable and reversible. The ligand affinity is similar (i.e., within 1 and 10 nM for the high-affinity site) to that observed in plasma membranes of liver, smooth muscle, etc. (for review, see Ref. 5), although the binding capacity is lower, resembling, for example, rabbit erythrocyte membrane where PGI2 and PGE1 purportedly modulate red cell deformability, controlling oxygen delivery to tissue through capillaries (7). Our data are, however, also consistent with the existence of a G protein-linked binding site of lower affinity. This may or may not be a separate entity; further molecular studies are required for its characterization.
Because PGE2,
PGE1,
PGD2, and
PGF2 have well-characterized
Na+-absorptive roles in the kidney
(26), we investigated their relative potencies in the lung alveolar
apical membrane by studying their ability to displace
[3H]PGE2
from the putative receptor site. Although
PGE2 and
PGE1 were approximately equally
effective in competing with
[3H]PGE2,
PGD2 showed a diminished effect,
followed by PGF2
. We identified
a similar differential in the PG effect on high-affinity GTPase
activity inhibition in the same preparation:
PGE2 and
PGE1 are roughly equipotent,
whereas PGD2 and
PGF2
(in that order) show an
apparently diminished effect on inhibition of G protein turnover. This
match between rank order of ligand binding and G protein turnover
inhibition is further suggestive of the presence of a functional PG
receptor working via G proteins in the fetal alveolar type II cell
apical membrane.
The ability of PGs to displace
[3H]PGE2
has been recently utilized to classify EP receptors (receptors
apparently specific for PGE2; see
Ref. 5). Although not studied here, we have previously shown that
~70% of the basal high-affinity GTPase activity in this preparation
is pertussis toxin insensitive. Interestingly, an EP receptor has been
shown to be coupled via the pertussis toxin-insensitive G protein
Gq (possibly one of the
functionally important G proteins in our system; see Ref. 21) in bovine
adrenal glands (22). Our observed rank order
(PGE2 = PGE1 > PGD2 > PGF2) for
[3H]PGE2
displacement is characteristic of the
EP3 subtype (5). Although
EP3 receptor mRNA is expressed in
many tissues, it is of relevance that expression is significant in both
kidney and lung (31).
Finally, we studied the effect of stimulating this G protein-linked PG receptor on Na+ transport into apical membrane vesicles. It is appropriate at this point to mention the caveat that agonist-dependent stimulation of the initial rate of 22Na+ uptake into vesicles represents data obtained from a pure system and may not replicate events at the complex level of the cells and in the animal. The system allows us, however, to study more specifically the regulation of conductive Na+ transport in type II pneumocytes while generating data that we expect will be interpretable in due course in the context of a functionally integrated preparation.
In apical membrane vesicles, PGE2
(1 µM) or GTP (100 µM) on their own had no significant effect on
the initial rate of
22Na+
uptake compared with control. In combination, however, they produced a
38% increase in this rate. Interestingly, this is not significantly different from the increase in initial rate achieved by irreversible G
protein activation alone with the nonhydrolyzable GTP analog GTPS.
Because all PG receptors are G protein linked, it follows that
stimulation of the alveolar prostanoid receptor is capable of fully
activating the G protein-mediated upregulation of lung alveolar
Na+ transport. Thus (as for the
renal Na+ absorptive process),
PGE2 receptors may prove to be an
important determinant of overall perinatal alveolar fluid homeostasis,
facilitating the clearance of excess lung fluid in preparation for
birth.
Although inhibition of G protein activity with PGs (23) and other
agonists (9) has been previously observed, we are the first to note the
apparent association of such inhibition with an upregulation of
cellular function. G protein-mediated signal transduction is not a
simple linear process but involves intricate cross talk between
different G protein-coupled pathways and between G protein-coupled
pathways and other signal transduction systems (29). G dimer
could regulate this interaction between G protein and the
Na+ channel, since maintaining the
G
-GTP state will hinder reassociation of the heterotrimeric G
protein and could facilitate possible G
-mediated stimulation of
Na+ transport. Also, both
stimulation and inhibition of G proteins regulate surfactant secretion
in the type II pneumocyte (25), and further studies are necessary to
relate the observations of downregulation of high-affinity GTPase
activity and stimulation of
Na+-channel function. We (21) and
other workers (9) have recently observed similar G protein turnover
inhibition induced by polyunsaturated fatty acids. Although others have
discussed possible mechanisms by which such an effect on G
proteins could be of functional importance by being transiently
inhibitory (thus allowing participation in a feedback regulatory
process), we have explored its relation to concomitant upregulation of
cellular function.
Neonatal respiratory distress syndrome continues to have a high mortality and morbidity despite the introduction of surfactant treatment (27). Novel therapeutic strategies directed toward lung alveolar fluid overload (a problem that coexists with surfactant depletion in respiratory distress syndrome) are likely to improve survival and reduce morbidity. A clear understanding of the cellular pathways that regulate Na+-driven absorption, like that described here of PG receptors, of lung fluid at birth is of crucial importance in the formulation of such strategies.
![]() |
ACKNOWLEDGEMENTS |
---|
We thank Craig Carr, Prof. Milligan (Biochemistry, Glasgow), Alan Monaghan, Debbie Baines, Mark Clunes, Lorraine Gambling, Craig Gould (Child Health, Dundee), and Margaret Gordon and Fiona Campbell (Rowett Research Institute, Aberdeen) for laboratory and/or statistical assistance.
![]() |
FOOTNOTES |
---|
This work was supported by Wellcome Trust Grants 042224/Z/94/Z and 039124/Z/4A. S. Mukhopadhyay was a recipient of the Wellcome Advanced Research Training Fellowship from the Wellcome Trust, UK.
Current addresses: G. F. Fyfe, Dept. of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar St., PO Box 3333, New Haven, CT 06510-6026; P. J. Kemp, Dept. of Physiology, Worsley Medical and Dental Building, University of Leeds, Leeds LS2 9JT, UK.
Address for reprint requests: S. Mukhopadhyay, Lung Membrane Transport Group, Dept. of Child Health, Ninewells Hospital and Medical School, Univ. of Dundee, Dundee DD1 9SY, UK.
Received 7 August 1997; accepted in final form 16 January 1998.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Barker, P. M.,
D. V. Walters,
M. Markiewicz,
and
L. B. Strang.
Development of the lung liquid reabsorptive mechanism in fetal sheep: synergism of triiodothyronine and hydrocortisone.
J. Physiol. (Lond.)
433:
435-449,
1991[Abstract].
2.
Bland, R. D.
Pathogenesis of pulmonary edema after premature birth.
Adv. Pediatr.
34:
175-222,
1987[Medline].
3.
Bradford, M. M.
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
Anal. Biochem.
72:
248-254,
1976[Medline].
4.
Cassin, S.
Effect of indomethacin on fetal lung liquid formation.
Can. J. Physiol. Pharmacol.
62:
157-159,
1984[Medline].
5.
Coleman, R. A.,
W. L. Smith,
and
S. Narumiya.
International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes.
Pharmacol. Rev.
46:
205-229,
1994[Medline].
6.
Dube, G. P.,
D. E. Mais,
J. A. Jakubowski,
K. A. Brune,
B. G. Utterback,
T. A. True,
L. E. Rinkema,
and
W. L. Kurtz.
In vitro characterisation of a novel TXA(2)/PGH(2) receptor ligand (S-145) in platelets and vascular and airway smooth muscle.
J. Pharmacol. Exp. Ther.
262:
784-791,
1992[Abstract].
7.
Dutta-Roy, A. K.,
L. Hoque,
and
B. J. Paterson.
Prostaglandin-E1-binding sites in rabbit erythrocyte membranes.
Eur. J. Biochem.
213:
1167-1173,
1993[Abstract].
8.
Fyfe, G. K.,
P. J. Kemp,
E. J. Cragoe, Jr.,
and
R. E. Olver.
Conductive cation transport in apical membrane vesicles prepared from fetal lung.
Biochim. Biophys. Acta
1224:
355-364,
1994[Medline].
8a.
Fyfe, G. K.,
P. J. Kemp,
and
R. E. Olver.
Conductive Na+ transport in fetal lung alveolar apical membrane vesicles is regulated by fatty acids and G proteins.
Biochim. Biophys. Acta
1355:
33-42,
1997[Medline].
9.
Glick, J.,
G. Santoyo,
and
P. J. Casey.
Arachidonate and related unsaturated fatty acids selectively inactivate the guanine nucleotide-binding regulatory protein, Gz.
J. Biol. Chem.
271:
2949-2954,
1996
10.
Grantham, J. J.,
and
J. Orloff.
Effect of prostaglandin E1 on the permeability response of the isolated collecting tubule to vasopressin, adenosine 3',5'-monophosphate, and theophylline.
J. Clin. Invest.
47:
1154-1161,
1968[Medline].
11.
Harris, D. A.
Spectrophotometry.
In: Spectrophotometry and Spectrofluorimetry, edited by D. A. Harris,
and C. L. Bashford. Oxford: IRL, 1987, p. 49-90.
12.
Hummler, E.,
P. Barker,
J. Gatzy,
F. Beermann,
C. Verdumo,
A. Schmidt,
R. Boucher,
and
B. C. Rossier.
Early death due to defective neonatal lung liquid clearance in alphaENAC-deficient mice.
Nat. Genet.
12:
325-328,
1996[Medline].
13.
Johnston, S. L.,
N. J. Freezer,
W. Ritter,
S. O'Toole,
and
P. H. Howarth.
Prostaglandin D2-induced bronchoconstriction is mediated only in part by the thromboxane prostanoid receptor.
Eur. Respir. J.
8:
411-415,
1995
14.
Kemp, P. J.,
G. C. Roberts,
and
C. A. R. Boyd.
Identification and properties of pathways for K+ transport in guinea-pig and rat alveolar epithelial type II cells.
J. Physiol. (Lond.)
476:
79-88,
1994[Abstract].
15.
Kitterman, J.,
G. Liggins,
J. Clements,
G. Campos,
C. Lee,
and
P. Ballard.
Inhibitors of prostaglandin synthesis, tracheal fluid, and surfactant in fetal lambs.
J. Appl. Physiol.
51:
1562-1567,
1981
16.
Lefkowitz, R. J.,
D. Mullikin,
C. L. Wood,
T. B. Gore,
and
C. Mukherjee.
Regulation of prostaglandin receptors by prostaglandins and guanine nucleotides in frog erythrocytes.
J. Biol. Chem.
15:
5295-5303,
1977.
17.
Light, D. B.,
D. A. Ausiello,
and
B. A. Stanton.
Guanine nucleotide-binding protein, ai-3, directly activates a cation channel in rat renal inner medullary collecting duct cells.
J. Clin. Invest.
84:
352-356,
1989[Medline].
18.
MacGregor, G. G.,
R. E. Olver,
and
P. J. Kemp.
Amiloride-sensitive Na+ channels in fetal type II pneumocytes are regulated by G proteins.
Am. J. Physiol.
267 (Lung Cell. Mol. Physiol. 11):
L1-L8,
1994
19.
McCray, P. B., Jr.,
and
J. D. Bettencourt.
Prostaglandins stimulate fluid secretion in human fetal lung.
J. Dev. Physiol. (Eynsham)
19:
29-36,
1993[Medline].
20.
McKenzie, F. R.
Basic techniques to study G-protein function.
In: Signal TransductionA Practical Approach (1st ed.), edited by G. Milligan. Oxford, UK: Oxford Univ. Press, 1992, p. 31-56.
21.
Mukhopadhyay, S.,
S. J. Ramminger,
M. McLaughlin,
L. Gambling,
R. E. Olver,
and
P. J. Kemp.
Direct modulation of G proteins by polyunsaturated fatty acids: a novel eicosanoid-independent regulatory mechanism in the developing lung.
Biochem. J.
326:
725-730,
1997[Medline].
22.
Negishi, M.,
S. Ito,
and
O. Hayaishi.
Prostaglandin E receptors in bovine adrenal medulla are coupled to adenylate cyclase via Gi and to phosphoinositide metabolism in a pertussis toxin-insensitive manner.
J. Biol. Chem.
264:
3916-3923,
1989
23.
Negishi, M.,
T. Namba,
Y. Sugimoto,
A. Irie,
T. Katada,
S. Narumiya,
and
A. Ichikawa.
Opposite coupling of prostaglandin E receptor EP2c with Gs and Go.
J. Biol. Chem.
268:
26067-26070,
1993
24.
Olver, R. E.,
C. A. Ramsden,
L. B. Strang,
and
D. V. Walters.
The role of amiloride-blockable sodium transport in adrenaline-induced lung liquid reabsorption in the fetal lamb.
J. Physiol. (Lond.)
376:
321-340,
1986[Abstract].
25.
Pian, M. S.,
and
L. G. Dobbs.
Activation of G proteins may inhibit or stimulate surfactant secretion in rat alveolar type II cells.
Am. J. Physiol.
266 (Lung Cell. Mol. Physiol. 10):
L375-L381,
1994
26.
Smith, W. L.
The eicosanoids and their biochemical mechanisms of action.
Biochem. J.
259:
315-324,
1989[Medline].
27.
Soll, R. F.,
and
M. C. McQueen.
Respiratory distress syndrome.
In: Effective Care of the Newborn Infant, edited by J. C. Sinclair,
and M. B. Bracken. Oxford, UK: Oxford Univ. Press, 1992, p. 325-328.
28.
Sonnenberg, W. K.,
and
W. L. Smith.
Regulation of cyclic-AMP metabolism in rabbit cortical collecting tubule by prostaglandins.
J. Biol. Chem.
263:
6155-6160,
1988
29.
Spiegel, A. M.
Specificity of receptor-effector coupling by G proteins.
In: G Proteins, edited by A. M. Spiegel,
T. L. Z. Jones,
W. F. Simonds,
and L. S. Weinstein. Austin, TX: Landes, 1994, p. 66-74.
30.
Stubbs, C. D.
Membrane fluidity: structure and dynamics of membrane lipids.
Essays Biochem.
19:
1-39,
1983[Medline].
31.
Sugimoto, Y.,
T. Namba,
A. Honda,
Y. Hayashi,
M. Negishi,
A. Ichikawa,
and
S. Narumiya.
Cloning and expression of a cDNA for mouse prostaglandin E receptor EP3 subtype.
J. Biol. Chem.
267:
6463-6466,
1992
32.
Wallen, L.,
D. Murai,
R. Clyman,
C. Lee,
F. Mauray,
P. Ballard,
and
J. Kitterman.
Meclofenamate does not affect lung development in fetal sheep.
J. Dev. Physiol.
12:
109-115,
1989[Medline].
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Visit Other APS Journals Online |