Identification of a Novel Gene Family Encoding Human
Liver-specific Organic Anion Transporter LST-1*
Takaaki
Abe
§¶,
Masayuki
Kakyo
§
,
Taro
Tokui§**,
Rie
Nakagomi**,
Toshiyuki
Nishio
,
Daisuke
Nakai**,
Hideki
Nomura
,
Michiaki
Unno
,
Masanori
Suzuki
,
Takeshi
Naitoh
,
Seiki
Matsuno
, and
Hiromu
Yawo
From the
Department of Neurophysiology,
1st
Department of Surgery, 
Department of
Pediatrics, Tohoku University School of Medicine, Sendai, 980-8575 and ** Analytical and Metabolic Research Laboratories, Sankyo Co.,
Ltd., Tokyo, 140-8710, Japan
 |
ABSTRACT |
We have isolated a novel liver-specific organic
anion transporter, LST-1, that is expressed exclusively in the human,
rat, and mouse liver. LST-1 is a new gene family located between the organic anion transporter family and prostaglandin transporter. LST-1
transports taurocholate (Km = 13.6 µM) in a sodium-independent manner. LST-1 also shows
broad substrate specificity. It transports conjugated steroids
(dehydroepiandrosterone sulfate, estradiol-17
-glucuronide, and
estrone-3-sulfate), eicosanoids (prostaglandin E2,
thromboxane B2, leukotriene C4, leukotriene
E4), and thyroid hormones (thyroxine, Km = 3.0 µM and triiodothyronine,
Km = 2.7 µM), reflecting hepatic multispecificity.
LST-1 is probably the most important transporter in human liver
for clearance of bile acids and organic anions because hepatic levels
of another organic anion transporter, OATP, is very low. This is also
the first report of the human molecule that transports thyroid hormones.
 |
INTRODUCTION |
One of the major function of the liver is the removal of various
endogenous and exogenous compounds from the circulation (1, 2). This
clearance process involves basolateral membrane transport systems that
mediate the hepatocellular uptake of bile acids, organic anions, and
organic cations (3, 4). One well studied class of substrates are the
bile acids. The uptake of taurocholate is mainly mediated by the
Na+/taurocholate cotransporting polypeptide (ntcp) in a
Na+-dependent manner (5). The uptake of other
bile acids (e.g. cholate) occurs predominantly via a
Na+-independent mechanism (2, 4). Some amount of
taurocholate is also transported by the Na+-independent
mechanism. This Na+-independent carrier system further
shows a broad substrate specificity transporting conjugated steroids,
cardiac glycosides, and other xenobiotics (4).
Initially, the organic anion transporter
(oatp)1 family (oatp1, oatp2,
oatp3) was considered to represent the Na+-independent
transporting mechanisms in the liver (6-8). Subsequently, a human
cDNA, termed OATP, was isolated (9). However, significant differences were found between human OATP and rat oatp family. First,
although the substrate specificities were qualitatively similar,
significant differences were found between human OATP- and rat oatp
family-mediated initial uptake rates and apparent Km
values (10, 11). Second, Northern blot analysis of the human OATP
showed considerably high expression in the brain, a pattern that is
different from any of the oatp family members. These findings strongly
suggest the existence of a different group of organic anion
transporters in human liver.
Here we report the isolation of a novel human organic anion
transporter, termed LST-1, which is expressed exclusively in the liver.
When expressed in Xenopus oocytes, many of the functional characteristics of LST-1 were identical to the multispecific
transporting mechanisms of human liver. These results suggest that
LST-1 is the predominant clearance mechanism of several endogenous and exogenous substrates in human liver.
 |
MATERIALS AND METHODS |
Isolation of the Human LST-1 cDNA--
The
GenBankTM data base dbEST was searched with all known
mammalian oatp family and the prostaglandin (PG) transporters (6-9, 12-14) using the TBLASTN algorithm. As a result, three independent clones that have weak to moderate similarity to both the oatp family
and the PG transporter were identified (GenBankTM accession
numbers H62893, T73863, and R29414). Polymerase chain reaction primers
were designed from each EST sequence, and the amplified products were
subcloned into pBluescript. A human liver cDNA library was
constructed by the
ZAPII vector (Stratagene) (15). 5 × 105 independent clones were screened with each EST clone
under high stringency. As a result, the signals hybridized with each
EST clone were identical with each other. In a series of screenings, 52 hybridization-positive clones were isolated, and the clone that had the
largest insert (pH1) was chosen for further analysis. The sequences
were determined using ABI PrismTM 377 DNA sequencer
(Perkin-Elmer).
Homology Analysis--
Multiple sequence alignments of amino
acid sequences and phylogenetic tree construction were carried out
using Clustal W (16). The phylogenetic trees were described by TreeView
(17).
Northern Blot Analysis--
Multiple tissue
NorthernTM blots containing 2 µg of human, rat, and mouse
mRNAs were purchased (CLONTECH). Filters were
hybridized with the 32P-labeled fragment of the
3'-untranslated region of pH1 (EcoRI-EcoRI, 838 base pairs) for human and with full-length cDNA of pH1 for rat and
mouse Northern blot analyses. For human OATP analysis, the
3'-untranslated region (HindIII-EcoRI, 830 base
pairs) was used to discriminate the cross-hybridization. In human
Northern blot analyses, filters were hybridized in a buffer containing 50% formamide, 5 × SSC (1× SSC = 0.15 M NaCl
and 0.015 M sodium citrate), 5 × Denhardt's
solution, and 1% SDS at 42 °C overnight, washed in 0.2× SSC, 1%
SDS at 65 °C for 1 h, and exposed to a film at
80 °C for
3 h (human LST-1) or 3 days (human OATP). For rat and mouse
Northern blot analyses, filters were hybridized in a buffer containing
25% formamide, 5× SSC, 5× Denhardt's solution, and 1% SDS at
42 °C overnight, washed in 2× SSC, 1% SDS at 55 °C for 1 h, and exposed to a film at
80 °C for overnight (mouse) or 4 days
(rat). The human
-actin probe was used to monitor the quality of the mRNAs.
Expression of LST-1 in Xenopus Oocytes--
The isolated clone
pH1 was linearized, and the capped cRNA was transcribed in
vitro with T7 RNA polymerase (Stratagene). Xenopus laevis oocytes were prepared as described previously (7). Briefly, defolliculated oocytes were microinjected with 10 ng of transcribed cRNA and were cultured for 72 h in a modified Barth's medium (88 mM NaCl, 1 mM KCl, 2.4 mM
NaHCO3, 0.3 mM
Ca(NO3)2, 0.41 mM
CaCl2, 0.82 mM MgSO4, 15 mM Hepes, pH 7.6) at 18 °C. Uptake of radiolabeled chemicals was measured in a medium containing 100 mM NaCl,
2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, 10 mM Hepes, pH 7.5. Oocytes were incubated in 100 µl of the same medium containing
radiolabeled substrate at room temperature. Uptake was terminated by
the addition of 3 ml of ice-cold uptake buffer, and the oocytes were
washed 3 times. The water-injected oocytes were used as controls. The statistical significance was tested by unpaired t test.
 |
RESULTS |
Isolation and Structural Analysis of LST-1--
The isolated
cDNA encoding human LST-1 consisted of 691 amino acids
(Mr 78.912), and the hydrophobicity analysis
(18) suggested the presence of 12 transmembrane domains (Fig.
1a). There are seven putative
N-glycosylation sites in the predicted extracellular loops,
one potential phosphorylation site for cAMP-dependent
protein kinase, and one potential phosphorylation site for protein
kinase C in the third cytosolic hydrophilic loop (19, 20). The sequence homology analysis revealed a moderate sequence similarity to both the
oatp family and the PG transporter, which is moderately related to the
oatp family. The overall amino acid sequence identities were 42.2% for
human OATP (9), 42.9% for rat oatp1 (6), 43.6% for rat oatp2 (7, 8),
43.9% for rat oatp3(7), 42.0% for rat OAT-K1 (12), 33.0% for rat PG
transporter (13), and 34.9% for human PG transporter (14). The
phylogenetic tree analysis by using the neighbor-joining and the
maximum-likelihood methods showed that LST-1 is positioned between the
oatp family and the PG transporter (Fig. 1b).

View larger version (46K):
[in this window]
[in a new window]
|
Fig. 1.
a, alignment of the deduced amino acid
sequence of LST-1 (GenBankTM accession number AF060500),
human OATP, and human PG transporter (PGT). The sequences
are aligned with single-letter notation by inserting gaps (-) to
achieve the maximum homology. The 12 putative transmembrane segments (I
to XII) were assigned on the basis of hydrophobicity analysis. Sequence
motifs for potential N-glycosylation sites
(triangles) and possible phosphorylation sites
(asterisks) are indicated. b, phylogenetic
relationship between LST-1, the oatp family, and PG transporter. The
phylogenetic tree was constructed using CLUSTAL W and TreeView
(http://taxonomy.zoology.gla.ac.uk/rod/treeview.html) using ungapped
regions and distance correction. Branch lengths are drawn to
scale.
|
|
Northern Blot Analyses--
Northern blot analysis of the LST-1
showed two bands (one major band at 3.0 kilonucleotides and one minor
band at 4.8 kilonucleotides) exclusively in the liver (Fig.
2a). No significant expression was detectable in any of the other tissues examined. The rat and mouse
Northern blot analyses with the human LST-1 probe also detected a
single band only in the liver (Fig. 2, b and c),
suggesting that LST-1 and the rat and mouse homologues are
liver-specific.

View larger version (38K):
[in this window]
[in a new window]
|
Fig. 2.
Northern blot analysis of the human LST-1
mRNA. a, human Multiple Tissue
NorthernTM blots (2 µg of Poly(A)+ RNAs) were
hybridized with the 3'-noncoding region (the 838 base pairs
EcoRI-EcoRI fragment) of the human LST-1. Rat
(b) and mouse (c) Multiple Tissue
NorthernTM blots (CLONTECH) were
hybridized with the full length of the human LST-1 under low
stringency. d, human Multiple Tissue NorthernTM
blots were hybridized with the HindIII-EcoRI (830 base pairs) fragment of human OATP, which has less than 45% homology
with both human LST-1 and human PG transporter. In a and
d, hybridization of each blot with -actin has been
further performed to ensure the quality of the mRNA. The size
marker (kilonucleotides) used was the RNA ladder.
|
|
Because Kullak-Ublick et al. (9) reported the presence of
human OATP transcript in the liver, Northern blot analysis for the
human OATP was further performed. The signals were detected only in the
brain at 8.0 and 2.8 kilonucleotides (Fig. 2d), indicating that the expression of OATP is negligible in human liver.
To confirm this, we re-screened the human liver cDNA library
filters that were used for isolating LST-1 with the human OATP probe.
All the signals detected with the human OATP probe were completely
overlapped with the positive signals detected by the LST-1 probe. To
further characterize the OATP-positive signals, we designed the
polymerase chain reaction primers at the 3'-noncoding region of human
OATP, and amplification was performed. Among 52 LST-1-positive signals,
no polymerase chain reaction positive band was detected. Because the
human liver library used was not amplified, each positive signal was
independent and tentatively represented the population of the original
human liver mRNA. These data revealed that LST-1 is exclusively
expressed in the human, rat, and mouse liver, whereas OATP is expressed
in the human brain.
Pharmacological Characterizations--
Based on the structural
similarities observed between the oatp family and the PG transporter,
we assumed that LST-1 can transport both organic anions
(i.e. taurocholate and conjugated steroids) and eicosanoids.
In the oocytes injected with LST-1 cRNA, [3H]taurocholate
was transported according to the saturation kinetics with an apparent
Km of 13.6 ± 5.6 µM (Fig.
3). This LST-1-mediated [3H]taurocholate uptake was not inhibited by replacing
the extracellular Na+ with choline (p > 0.1), reflecting the Na+-independent fraction in human
liver. The LST-1-expressing oocytes also significantly transported
conjugated steroids dehydroepiandrosterone sulfate,
estradiol-17
-glucuronide, and estrone-3-sulfate (Table I). In contrast, unconjugated steroids
such as aldosterone, estradiol, and testosterone were not
transported.

View larger version (11K):
[in this window]
[in a new window]
|
Fig. 3.
Transport of taurocholate in LST-1-expressing
oocytes. The transport rates of [3H]taurocholate for
the LST-1 cRNA-injected oocytes were measured (20 min). From all uptake
values, nonspecific uptake into water-injected oocytes was subtracted.
A representative of three experiments is shown. The values indicated
are means ±S.E. of 5~9 oocyte determinations.
|
|
View this table:
[in this window]
[in a new window]
|
Table I
Uptake of 3H-labeled various compounds by LST-1-expressing
oocytes
The uptake experiments were performed at the concentration indicated
for 60 min. Values are mean ±S.E. of 8~15 oocytes determinations.
The significance between water-injected and LST-1-cRNA-injected oocytes
was determined by unpaired t test.
|
|
Moreover, the oocytes injected with LST-1 cRNA transported PG
E2, thromboxane B2, leukotriene C4,
and leukotriene E4 (Table I). On the other hand, no
arachidonic acid uptake was detected.
We have previously reported that oatp2 and oatp3 transport both
thyroxine (T4) and triiodothyronine (T3) (7). The LST-1 cRNA-injected
oocytes significantly transported [125I]T4 and
[125I]T3 in a saturable manner. The apparent
Km values for [125I]T4 and
[125I]T3 were 3.0 ± 1.3 µM and
2.7 ± 1.1 µM, respectively (Fig.
4, a and b). These
LST-1-mediated T4 and T3 uptakes were also Na+-independent
(data not shown). Thus, these data demonstrated that LST-1 encodes a
human liver-specific multifunctional transporter that transports
taurocholate, conjugated steroids, eicosanoids, and thyroid hormones in
accordance with the structural characteristics.

View larger version (9K):
[in this window]
[in a new window]
|
Fig. 4.
Transport of thyroid hormones in
LST-1-expressing oocytes. The transport rates of T4 (a)
and T3 (b) for the LST-1 cRNA-injected oocytes were measured
(20 min). A representative of three experiments is shown. The values
indicated are means ±S.E. of 8~15 oocyte determinations.
|
|
 |
DISCUSSION |
The present study describes the isolation of a new gene family
encoding human liver-specific organic anion transporter, LST-1. LST-1
appears to be an essential transporter in human liver for the following reasons.
LST-1 Is a Member of a Novel Super Gene Family Expressed in the
Liver--
A comparison of the LST-1 amino acid sequence to that of
human OATP and PG transporter revealed that, although the transmembrane regions and its surrounded area are moderately conserved, the N- and
C-terminal cytoplasmic regions are completely different (Fig.
1a). The phylogenetic tree analysis also revealed that LST-1 is branched between human OATP and PG transporter (Fig. 1b).
Therefore, we propose LST-1 as a novel gene family.
Northern blot analysis showed that the LST-1 mRNA is exclusively
expressed in human liver (Fig. 2a). The rat and mouse
Northern blot analyses with LST-1 as a probe also detected a single
band only in the liver (Fig. 2, b and c). In rat,
four oatp family members have been reported (6-8, 12). Among these,
oatp1, oatp2, and oatp3 are expressed in the liver, but their
expressions are not liver-specific. The PG transporter is also widely
distributed (13, 14). These data strongly suggest that human LST-1 is not the counterpart of the oatp family or the PG transporter, but it
belongs to another new super gene family exclusively expressed in the liver.
Human Organic Anion Transporters Distribute in a Organ-specific
Manner--
Northern blot analysis using the 3'-noncoding region of
human OATP detected signals only in the brain (Fig. 2d).
Although a previous study showed a rather broad distribution (9), this discrepancy is probably because of the cross-hybridization of the
less-specific probe. Thus, in human, OATP appears not to be the
principal organic anion transporter in the liver but to be the main
transporter in the brain. These data further suggest that, in human,
the organic anion transporters are assumed to be expressed in an
organ-specific manner.
Pharmacological Properties Are Similar to Human
Liver--
Functional analysis for LST-1 revealed that LST-1
transported taurocholate (Km, 13.6 µM)
in a Na+-independent manner (Fig. 3). This value is
approximately two to four times lower than those of the oatp family and
human OATP (7-9, 21), whereas it is comparable with that of the human hepatocyte when extracellular Na+ was removed (22). These
data suggest that LST-1 is the molecule representing the
Na+-independent bile acid uptake in human liver.
Furthermore, in the liver, interspecies differences of taurocholate
uptake between rat and human liver have been reported (4, 22). These
functional differences can be explained by the difference in the major
organic anion transporter molecule in rat and human liver: LST-1 in
human and oatp family members in rat.
The oatp family transports bile acids but does not transport
eicosanoids (PG E2, PG
F2
, and thromboxane
B2) (21, 23). On the other hand, the PG transporter
transports PG E1, PG E2, PG
F2
, and thromboxane B2 but does
not transport taurocholate (13, 14, 24). Our study shows that the
substrate specificities of the LST-1 are intermediate; it transports
taurocholate, conjugated steroids (dehydroepiandrosterone sulfate,
estradiol-17
-glucuronide, and estrone-3-sulfate) and eicosanoids (PG
E2, thromboxane B2, leukotriene C4,
and leukotriene E4) (Figs. 3 and 4; Table I). It is
speculated that this wide substrate specificity would be explained by
the structure of the LST-1, because LST-1 is structurally located
intermediately between the oatp family and the PG transporter.
Our previous data revealed that both rat oatp2 and oatp3 transport
thyroid hormones (7). LST-1 cRNA-injected oocytes transported T4 and T3
(Fig. 4, a and b). In human liver,
carrier-mediated transport of thyroid hormone has been predicted (25,
26). Thus, this is the first report identifying a human molecule that transports thyroid hormone, and these findings should be a tool for
understanding the delivery of thyroid hormone to tissue in human
(27).
Taken together, it is concluded that in human, LST-1 should be the
essential molecule for transporting bile acids and organic anions in
the liver, reflecting the multispecificity of the
Na+-independent clearance mechanism in vivo.
So far, in human, the Na+-independent fraction of bile acid
and organic anion transport in the liver have been discussed by using
human OATP as a responsible molecule. However, the present study
reveals that LST-1 may actually be the essential molecule in human
liver, and the hepatic expression of human OATP is negligible. Further
studies of LST-1 should provide new insight into bile acid formation
and greater understanding of the pathogenesis of the diseases such as
cholestasis (28), hyperbilirubinemia (29), and thyroid hormone
resistance (Refetoff's syndrome) (30). Our findings may also be a new
guide to develop the liver-specific drug delivery system and
liver-specific chemotherapy (31).
 |
ACKNOWLEDGEMENT |
We thank to Dr. Kazuo Nunoki for discussions.
 |
FOOTNOTES |
*
This work was supported in part by research grants from the
Ministry of Education, Science, and Culture of Japan, the Yamanouchi Foundation for Research on Metabolic Disorders, the Nishimiya Foundation, the Tokyo Biochemical Research Foundation, the Japan Research Foundation for Clinical Pharmacology, and the Inamori Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF060500.
§
These authors contributed equally to this study.
¶
To whom correspondence should be addressed: Dept. of
Neurophysiology, Tohoku University School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan. Tel: +81-22-717-8153; Fax:
+81-22-717-8154; E-mail: takaabe{at}mail.cc.tohoku.ac.jp.
 |
ABBREVIATIONS |
The abbreviations used are:
ntcp, Na+/taurocholate cotransporting polypeptide;
oatp, organic
anion-transporting polypeptide;
PG, prostaglandin;
T4, thyroxine;
T3, 3,5,3'- triiodo-L-thyronine.
 |
REFERENCES |
-
Scharschmidt, B. F.,
Waggoner, J. G.,
and Berk, P. D.
(1975)
J. Clin. Invest.
56,
1280-1292[Medline]
[Order article via Infotrieve]
-
Tiribelli, C.,
Lunazzi, G. C.,
and Sottocasa, G. L.
(1990)
Biochim. Biophys. Acta
1031,
261-275[Medline]
[Order article via Infotrieve]
-
Wolkoff, A. W.
(1996)
Semin. Liver Dis.
16,
121-127[Medline]
[Order article via Infotrieve]
-
Müller, M.,
and Jansen, P. L. M.
(1997)
Am. J. Physiol.
272,
G1285-G1303[Abstract/Free Full Text]
-
Hagenbuch, B.,
Stieger, B.,
Foguet, M.,
Lübbert, H.,
and Meier, P. J.
(1991)
Proc. Natl. Acad. Sci. U. S. A.
88,
10629-10633[Abstract]
-
Jacquemin, E.,
Hagenbuch, B.,
Stieger, B.,
Wolkoff, A. W.,
and Meier, P. J.
(1994)
Proc. Natl. Acad. Sci. U. S. A.
91,
133-137[Abstract]
-
Abe, T.,
Kakyo, M.,
Sakagami, H.,
Tokui, T.,
Nishio, T.,
Tanemoto, M.,
Nomura, H.,
Hebert, S. C.,
Matsuno, S.,
Kondo, H.,
and Yawo, H.
(1998)
J. Biol. Chem.
273,
22395-22401[Abstract/Free Full Text]
-
Noé, B.,
Hagenbuch, B.,
Stieger, B.,
and Meier, P. J.
(1997)
Proc. Natl. Acad. Sci. U. S. A.
94,
10346-10350[Abstract/Free Full Text]
-
Kullak-Ublick, G.-A.,
Hagenbuch, B.,
Stieger, B.,
Schteingart, C. D.,
Hofmann, A. F.,
Wolkoff, A. W.,
and Meier, P. J.
(1995)
Gastroenterology
109,
1274-1282[Medline]
[Order article via Infotrieve]
-
Bossuyt, X.,
Müller, M.,
and Meier, P. J.
(1996)
J. Hepatol.
25,
733-738[CrossRef][Medline]
[Order article via Infotrieve]
-
Meier, P. J.,
Eckhardt, U.,
Schroeder, A.,
Hagenbuch, B.,
and Stieger, B.
(1997)
Hepatology
26,
1667-1677[Medline]
[Order article via Infotrieve]
-
Saito, H.,
Masuda, S.,
and Inui, K.
(1996)
J. Biol. Chem.
271,
20719-20725[Abstract/Free Full Text]
-
Kanai, N.,
Lu, R.,
Satriano, J. A.,
Bao, Y.,
Wolkoff, A. W.,
and Schuster, V. L.
(1995)
Science
268,
866-869[Medline]
[Order article via Infotrieve]
-
Lu, R.,
Kanai, N.,
and Schuster, V.
(1996)
J. Clin. Invest.
98,
1142-1149[Abstract/Free Full Text]
-
Abe, T.,
Sugihara, H.,
Nawa, H.,
Shigemoto, R.,
Mizuno, N.,
and Nakanishi, S.
(1992)
J. Biol. Chem.
267,
13361-13368[Abstract/Free Full Text]
-
Thompson, J. D.,
Higgins, D. G.,
and Gibson, T. J.
(1994)
Nucleic Acids Res.
22,
4673-4680[Abstract]
-
Page, R. D. M.
(1996)
Comput. Appl. Biosci.
12,
357-357[Medline]
[Order article via Infotrieve]
-
Kyte, J.,
and Doolittle, R. F. J.
(1982)
J. Mol. Biol.
157,
105-132[Medline]
[Order article via Infotrieve]
-
Kemp, B. E.,
and Pearson, R. B.
(1990)
Trends Biol. Sci.
15,
342-346
-
Kennelly, P. J.,
and Krebs, E. G.
(1991)
J. Biol. Chem.
266,
15555-15558[Free Full Text]
-
Kullak-Ublick, G.-A.,
Hagenbuch, B.,
Stieger, B.,
Wolkoff, A. W.,
and Meier, P. J.
(1994)
Hepatology
20,
411-416[Medline]
[Order article via Infotrieve]
-
Sandker, G. W.,
Weert, B.,
Olinga, P.,
Wolters, H.,
Slooff, M. J. H.,
Meijer, D. K. F,
and Groothuis, G. M. M.
(1994)
Biochem. Pharmacol.
47,
2193-3200[CrossRef][Medline]
[Order article via Infotrieve]
-
Kanai, N.,
Lu, R.,
Wolkoff, A. W.,
and Schuster, V. L.
(1996)
Am. J. Physiol.
270,
F319-F325[Abstract/Free Full Text]
-
Schuster, V. L.
(1998)
Anni. Rev. Physiol.
60,
221-241[CrossRef][Medline]
[Order article via Infotrieve]
-
Kragie, L.,
and Doyle, D.
(1992)
Endocrinology
130,
1211-1216[Abstract]
-
De Jong, M.,
Docter, R.,
Bernard, B. F.,
Van der Heijden, J. T. M.,
van Toor, H.,
Krenning, E. P.,
and Hennemann, G.
(1994)
Am. J. Physiol.
266,
E768-E775[Abstract/Free Full Text]
-
Pardridge, W. M.
(1998)
in
Handbook of Physiology, Section 7: The Endocrine System Volume I: Cellular Endocrinology (Conn, M., ed), pp. 335-382, Oxford University Press, Oxford
-
Dumont, M.,
Jacquemin, E.,
D'Hont, C.,
Descout, C.,
Cresteil, D.,
Haouzi, D.,
Desrochers, M.,
Stieger, B.,
Hadchouel, M.,
and Erlinger, S. E.
(1997)
J. Hepatol.
27,
1051-1056[CrossRef][Medline]
[Order article via Infotrieve]
-
Becker, S. D.,
and Lamont, J. T.
(1988)
Semin. Liver Dis.
8,
183-190[Medline]
[Order article via Infotrieve]
-
Refetoff, S.,
Weiss, R. E.,
and Usala, S. J.
(1993)
Endocrine Rev.
14,
348-399[Medline]
[Order article via Infotrieve]
-
Kullak-Ublick, G.-A.,
Glasa, J.,
Böker, C.,
Oswald, M.,
Grützner, U.,
Hagenbuch, B.,
Stieger, B.,
Meier, P. J.,
Beuers, U.,
Kramer, W.,
Wess, G.,
and Paumgartner, G.
(1997)
Gastroenterology
113,
1295-1305[Medline]
[Order article via Infotrieve]
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.