Endocrinology Vol. 142, No. 10 4251-4255
Copyright © 2001 by The Endocrine Society
Cholecystokinin Stimulates Aldosterone Secretion from Dispersed Rat Zona Glomerulosa Cells, Acting Through Cholecystokinin Receptors 1 and 2 Coupled with the Adenylate Cyclase-Dependent Cascade
Ludwik K. Malendowicz,
Magdalena Nowak,
Lucia Gottardo,
Cinzia Tortorella,
Mariola Majchrzak and
Gastone G. Nussdorfer
Department of Histology and Embryology, School of Medicine (L.K.M.,
M.N., M.M.), PL-60781 Poznan, Poland; and Department of Human
Anatomy and Physiology, Section of Anatomy, University of Padua (L.G.,
C.T., G.G.N.), I-35121 Padua, Italy
Address all correspondence and requests for reprints to: Prof. G. G. Nussdorfer, Department of Human Anatomy and Physiology, Section of Anatomy, Via Gabelli 65, I-35121 Padova, Italy. E-mail:
ggnanat{at}ipdunidx.unipd.it
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Abstract
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Cholecystokinin is a regulatory peptide, that acts through two
subtypes of receptors, 1 and 2. RT-PCR demonstrated the expression of
both cholecystokinin receptors 1 and 2 genes in the zona glomerulosa,
but not the zona fasciculata-reticularis, of rat adrenals.
Autoradiography demonstrated the presence of abundant
[125I]cholecystokinin-binding sites in the zona
glomerulosa, but not the zona fasciculata-reticularis, which were
displaced by both cholecystokinin receptor 1- and 2-selective
antagonists (cholecystokinin 1-A and 2-A). Cholecystokinin increased
basal aldosterone secretion from dispersed zona glomerulosa cells
without affecting corticosterone secretion from zona
fasciculata-reticularis cells. The aldosterone response to
cholecystokinin was blunted by cholecystokinin 1-A and 2-A, which when
added together abolished it. ACTH-stimulated aldosterone production was
not affected by cholecystokinin; in contrast, cholecystokinin
potentiated aldosterone response to both angiotensin II and
K+. Cholecystokinin enhanced cAMP, but not IP3,
release by dispersed zona glomerulosa cells. The aldosterone response
to cholecystokinin was abolished by the adenylate cyclase inhibitor
SQ-22536 and the PKA inhibitor H-89, but not by either the PLC
inhibitor U-73122 or the PKC inhibitor calphostin C. In conclusion, our
study provides evidence that cholecystokinin, acting through
cholecystokinin receptors 1 and 2 coupled with the adenylate
cyclase/PKA cascade, exerts a sizeable secretagogue action on rat zona
glomerulosa cells.
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Introduction
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CHOLECYSTOKININ (CCK) IS a regulatory
peptide, widely distributed in the central nervous system and
peripheral organs and tissues, which plays a role in the regulation of
satiety, anxiety, and neuroendocrine system (1). CCK
exerts its biological effects through two main G protein-coupled
receptor subtypes, named CCK1-R and CCK2-R (formerly CCKA alimentary
and CCKB brain receptors) (2).
Evidence has accumulated that CCK stimulates the activity of the
hypothalamo-pituitary-adrenal axis by enhancing ACTH and glucocorticoid
secretion through the activation of both CCK1-R and CCK2-R
(3, 4, 5, 6, 7, 8, 9) CCK immunoreactivity has been detected in some
substance P-positive nerve fibers of the human and guinea pig adrenal
cortex and medulla (10), and the presence of CCK1-R was
found in cultured bovine adrenomedullary cells (11). Due
to the complex paracrine interactions between cortex and medulla
(12), these last findings could suggest a direct action of
CCK on the adrenal cortex. However, investigations on this topic are
scarce, and their results disappointing. In fact, CCK has been reported
to exert no sizeable effect on basal and ACTH-stimulated corticosterone
secretion from dispersed rat adrenocortical cells (13).
Therefore, it seemed worthwhile to investigate whether adrenocortical
cells express CCK receptors, and whether CCK affects their secretory
activity in vitro.
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Materials and Methods
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Animals and reagents
Adult female Wistar rats (150 ± 10 g BW) were kept
under a 12-h light, 12-h dark cycle (illumination onset at 0800 h)
at 23 C and maintained on a standard diet and tap water ad
libitum. The CCK octapeptide and [125I]CCK
octapeptide were purchased from Peninsula Laboratories, Inc. (St. Helens, UK). The dipeptoid CCK1-R antagonist
PD-140,548 N-methyl-D-glucamine
(CCK1-A) and the selective CCK2-R antagonist PD-135,158
N-methyl-D-glucamine (CCK2-A)
(2) were obtained from Research Biochemicals International (Natick, MA). The adenylate cyclase inhibitor
SQ-22536, the PLC inhibitor U-73122, and the PKA and PKC inhibitors
H-89 and calphostin C (14) were purchased from
BIOMOL Research Laboratories, Inc. (Milan, Italy).
ACTH-(1–24), angiotensin II (Ang-II), 3-isobutyl-1-methylxantine, BSA,
and other laboratory reagents were provided by Sigma (St.
Louis, MO).
RT-PCR
The adrenal glands of six rats were gently decapsulate to
separate zona glomerulosa (ZG) and then were halved. Each adrenal half
was enucleated to separate adrenal medulla from inner cortical zonae
fasciculata and reticularis (ZF/R). RNA was extracted from ZG and ZF/R
preparations with the guanidium isothiocyanate method, and total RNA
was reversed transcribed to cDNA, as previously detailed
(15). The 5'- and 3'-primers used for OX1-R and OX2-R
mRNAs were selected with Oligo 3.0 primer analysis software on the
basis of GenBank cDNA sequences of rat origin (16, 17, 18):
CCK1-R: sense (nucleotides 317–337),
5'-AGTCTGCACTGCAGATTCTCC-3'; and antisense (nucleotides 791–811),
5'-TAGCGTCACTTGGCAACAGG-3'; and CCK2-R: sense (nucleotides 1276–1297),
5'-CACTTGCTGAGCTACGTCTCCG-3'; and antisense (nucleotides 1848–1870),
5'-GTCACT TCTGCACTAGGCTATGG-3'. The primers used for
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA were selected
according to the method described by Tso et al.
(19). In a Delphi 100 Thermal Cycler (Oracle Biosystem,
MJ Research, Inc., Waterston, MA) we used a denaturation
step at 94 C for 45 sec, an annealing step at 61 C for 25 sec, and an
extension step at 72 C for 2 min for a total of 34 cycles, with a final
extension step at 72 C for 15 min. To rule out the possibility of
amplifying genomic DNA, in some experiments PCR was performed without
prior RT of the RNA. Detection of the PCR amplification products was
first carried out by size fractionation on 2% agarose gel
electrophoresis. The amplification products were of the expected size,
i.e. 495, 595, and 585 bp for CCK1-R, CCK2-R, and GAPDH,
respectively. After purification using the QIA quick PCR purification
kit (QIAGEN, Hilden, Germany), PCR products were
identified by sequencing on an Alf sequencer (Pharmacia Biotech, Freiburg, Germany).
Autoradiography
Adrenal glands taken from six rats were immediately frozen at
-30 C by immersion in isopentane and stored at -80 C. Frozen sections
(10–15 µm thick) were cut in a digital cryostat (model 1720,
Leitz, Rockleigh, NJ) at -20 C and processed as
previously detailed (20). CCK-binding sites were labeled
in vitro by incubation for 120 min at 37 C with
10-7 M
[125I]CCK, and aspecific binding was checked by
addition of 10-6 M cold
CCK. The ability of CCK1-A and CCK2-A to displace
[125I]CCK binding was evaluated by adding each
of them at a concentration of 10-6
M. The reaction was stopped by washing the
samples three times in 50 mM Tris-HCl buffer.
After rinsing, the sections were rapidly dried, fixed in
paraformaldehyde vapors at 80 C for 120 min, and coated with NTB2
nuclear emulsion (Eastman Kodak Co., Rochester, NY).
Autoradiograms were exposed for 2 wk at 4 C, then developed with
undiluted Kodak D19 developer. Three unstained
autoradiograms obtained from six adrenals were analyzed by
computer-assisted densitometry, with a camera-connected microscope and
a computer equipped with a software specifically written for this
purpose (Studio Casti Imaging, Venice, Italy) (20). For
each autoradiogram, 10 areas of ZG (
36,000 pixels each) were
analyzed. The [125I]CCK binding density of the
gland connective capsule was taken as the background.
Steroid hormone secretion
Dispersed ZG and ZF/R cells were obtained from adrenal
preparations (see above) by sequential collagenase digestion and
mechanical disaggregation (20). ZF/R cell contamination of
ZG cell preparation, as evaluated by phase microscopy, was less than
5%, and the viability of dispersed cells, as checked by the trypan
blue exclusion test, was greater than 92%. Dispersed cells obtained
from eight rats were pooled to obtain a single cell suspension, and six
cell suspensions for each incubation experiment were used. Aliquots of
each cell suspension (105 cells/ml, in
Krebs-Ringer bicarbonate buffer with 0.3% glucose and 0.2% BSA) were
incubated as follows: 1) CCK (from
10-12–10-6
M) alone and in the presence of 10-9
M ACTH-(1–24), 10-9 M
Ang-II, or 10 mM K+; 2) CCK1-A or
CCK2-A (10-6 M) alone and in the
presence of 10-6 M CCK; and 3) CCK
(10-6 M) alone and in the presence
of 10-4 M SQ-22536,
10-5 M H-89,
10-5 M U-73122, or
10-5 M calphostin C. The incubation
was carried out in a shaking bath at 37 C for 60 min in an atmosphere
of 95% air-5% CO2. At the end of the
experiment, the incubation tubes were centrifuged at 4 C, and
supernatants were stored at -80 C. Aldosterone and corticosterone were
extracted from the incubation medium and purified by HPLC
(21). Their concentrations were measured by RIA, as
previously detailed (22). Intra- and interassay
coefficients of variation were: aldosterone, 5.5% and 7.1%; and
corticosterone, 7.6% and 9.3%, respectively.
cAMP and IP3 production
Dispersed cells were incubated, as described above, for 10 min
with CCK or PG (10-6 M), ACTH
(10-9 M), and Ang-II
(10-9 M) alone or in the presence of
10-4 M SQ-22536 and
10-5 M U-73122. In the case of cAMP
assay, the phosphodiesterase inhibitor 3-isobutyl-1-methylxantine
(10-4 M) was added to prevent cAMP
metabolism. cAMP was extracted by incubating the medium with 0.1
N HCl for 20 min at 4 C. The HCl extract was then
neutralized, and the cAMP concentration was determined following the
protocol developed by Amersham Pharmacia Biotech for
Biotrak TRK 432 (Little Chalfont, UK; sensitivity, 1 pmol/liter; intra-
and interassay variations, 5.3% and 6.6%, respectively).
IP3 was extracted by the trichloroacetic acid
method and purified by Amprep SAX-minicolumn chromatography, and its
concentration was measured by RIA. The procedure followed the protocol
developed by Amersham Pharmacia Biotech (Biotrak TRK 1000;
sensitivity, 2 pmol/liter; intra- and interassay variations, 6.8% and
8.1%, respectively).
Statistics
Data were averaged per experimental group and expressed as the
mean ± SEM of six independent experiments. The
statistical comparison of results was performed by ANOVA, followed by
the multiple range test of Duncan.
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Results
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RT-PCR allowed the detection of both CCK1-R and CCK2-R mRNAs in
the ZG, but not ZF/R, of the rat adrenal cortex (Fig. 1
). Autoradiography demonstrated the
presence of [125I]CCK-binding sites in the ZG
and adrenal medulla, but not ZF/R (Fig. 2A). Binding was eliminated by cold CCK
(data not shown) and was markedly decreased by both CCK1-A and CCK2-A
(Fig. 2, B and C), which when added together completely displaced it
(Fig. 2D). Quantitative densitometry confirmed these qualitative
descriptions as far as ZG is concerned (Fig. 3).
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Figure 1. Ethidium bromide-stained 2% agarose gel showing
cDNA amplified with rat CCK receptor and GAPDH primers from RNA of ZG
and ZF/R of the adrenal cortex of three rats (R1–R3). Lanes 1 were
loaded with 200 ng of a size marker (marker VIII; Roche Molecular Biochemicals, Mannheim, Germany). The amplified fragments were
of the expected sizes: 495 bp for OX1-R, 595 bp for OX2-R, and 585 bp
for GAPDH. No amplification of PCR mixture with water instead of RNA or
without prior RT of the OX1-R and OX2-R mRNAs is shown.
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Figure 2. Autoradiograms of hematoxylin-eosin-stained frozen
sections of rat adrenal gland incubated with 10-7
M [125I]CCK; binding is present in both ZG
and AM (A). Both CCK1-A (B) and CCK2-A (10-6
M; C) partially displace binding, and when added together
completely eliminate binding (D). AM, Adrenal medulla. Magnification,
x80.
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Figure 3. Evaluation by quantitative densitometry of
10-7 M [125I]CCK binding in the
rat ZG (total binding, TB) and of its displacement by 10-6
M cold CCK, CCK1-A, CCK2-A, and CCK1-A plus CCK2-A.
Bars show the mean ± SEM (n = 6).
**, P < 0.01 vs. background (BG)
value; A, P < 0.01 vs.
TB value.
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CCK concentration-dependently increased basal aldosterone secretion
from ZG cells; the concentration of 10-6
M elicited a 2.2-fold increase. Corticosterone production
by ZF/R cells was not affected by CCK (Fig. 4). CCK1-A and CCK2-A blunted the
aldosterone response to 10-6 M CCK
and when added together abolished it (Fig. 5). CCK (10-6
M) did not affect the aldosterone response to ACTH, but
evoked a small, but significant, increase in the responses to both
Ang-II and K+ (Fig. 6).
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Figure 4. Effects of CCK on basal aldosterone (left
panel) and corticosterone (right panel)
secretion from dispersed rat ZG and ZF/R cells, respectively. Data are
the mean ± SEM (n = 6). *, P
< 0.05; **, P < 0.01 [vs. the
respective control (C) group].
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Figure 5. Effects of 10-6 M CCK1-A
and/or CCK2-A on basal and CCK (10-6
M)-stimulated aldosterone secretion from dispersed rat ZG
cells. Bars show the mean ± SEM (n = 8). *,
P < 0.05; **, P < 0.01
(vs. the respective baseline value). a,
P < 0.05; A, P <
0.01 (vs. the respective control value).
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Figure 6. Effects of CCK on 10-9 M
ACTH-, 10-9 M Ang-II-, or 10 mM
K+-stimulated aldosterone secretion from dispersed rat ZG
cells. Data are the mean ± SEM (n = 6). *,
P < 0.05; **, P < 0.01
[vs. respective control (C) value]. Baseline values
are shown on the y-axes.
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ACTH and Ang-II (10-9 M) increased
cAMP and IP3 production by dispersed ZG cells,
and their effects were annulled by 10-4
M SQ-22536 and 10-5 M
U-73122, respectively (Figs. 7 and 8). CCK (10-6
M) enhanced cAMP, but not IP3,
release by dispersed ZG cells (Figs. 7 and 8). The cAMP response to CCK
was decreased by both 10-6 M CCK1-A
and CCK2-A and was abrogated by the simultaneous addition of the two
antagonists (Fig. 7). The aldosterone response of dispersed ZG cells to
10-6 M CCK was abolished by either
10-4 M SQ-22536 or
10-5 M H-89 and was unaffected by
10-5 M U-73122 or calphostin C (Fig. 9).
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Figure 7. Effects of 10-9 M ACTH
(left panel) and 10-6
M CCK (right panel) on cAMP release from
dispersed rat ZG cells. The effect of ACTH is annulled by
10-4 M SQ-22536, and that of CCK is annulled
by 10-6 M CCK1-A and/or CCK2-A.
Bars show the mean ± SEM (n = 6).
**, P < 0.01 (vs. respective
control value). a, P < 0.05;
A, P < 0.01 (vs. ACTH
or CCK value).
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Figure 8. Effect of 10-9 M Ang-II
(left panel) and 10-6
M CCK (right panel) on IP3
release from dispersed rat ZG cells. The effect of Ang-II is annulled
by 10-5 M U-73122. Bars show
the mean ± SEM (n = 6). **,
P < 0.01 vs. the respective control
value. A, P < 0.01 vs.
Ang-II value.
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Figure 9. Effects of 10-4 M
SQ-22536, 10-5 M H-89, 10-5
M U-73122, and 10-5 M
calphostin C on basal and CCK (10-6
M)-stimulated aldosterone secretion from dispersed rat ZG
cells. Bars show the mean ± SEM
(n = 8). **, P < 0.01 vs. the
respective baseline value. A, P < 0.01
vs. the respective control value.
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Discussion
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Our investigation provides the first evidence that rat adrenal ZG
expresses CCK1-R and CCK2-R and is provided with CCK-binding sites,
whose activation enhances aldosterone secretion. In fact, both CCK1-A
and CCK2-A blunt the aldosterone response to CCK. The lack of CCK
receptor gene expression and CCK-binding sites in ZF/R cells and of
their corticosterone response to CCK is in keeping with the earlier
observations by Porter and Sander (13).
Of interest, CCK evoked a mild potentiation of Ang-II- and
K+-stimulated aldosterone secretion, without
affecting the response to ACTH. This finding suggests that CCK and ACTH
share the same mechanism of action. The signaling mechanism of ACTH
mainly involves activation of the adenylate cyclase-dependent cascade
(23). Although it is currently accepted that CCK1-R and
CCK2-R are coupled with both adenylate cyclase- and PLC-dependent
cascades in many cell systems (2), it appears legitimate
to suggest that the aldosterone secretagogue effect of CCK only
involves activation of the adenylate cyclase-PKA cascade in rat ZG
cells. This contention is supported by the demonstration that CCK
enhances cAMP, but not IP3, production by ZG
cells, and that the selective adenylate cyclase and PKA inhibitors
SQ-22536 and H-89 abolish the aldosterone response to CCK. SQ-22536 and
H-89 per se do not induce significant changes in basal
aldosterone secretion over 60 min of static incubation, which makes it
unlikely that their effect is due to a nonspecific toxic lesion of the
steroidogenic machinery. Conversely, the lack of effect of U-73122 and
calphostin C rules out the involvement of the PLC/PKC-dependent cascade
in the aldosterone response to CCK. Taken together, the present
findings indicate that CCK, acting through CCK1-R and CCK2-R coupled
with the adenylate cyclase/PKA cascade, exerts a marked secretagogue
action on rat ZG cells.
The functional relevance of the present findings remains to be
assessed, because the aldosterone secretagogue action of CCK appears to
be very low compared with that of other classic agonists of ZG cells.
However, not only are CCK-positive nervous fibers contained in the
mammalian adrenal cortex (10), but CCK immunoreactivity
was detected in adrenal venous blood (24, 25) and in
pheochromocytomas (26). Thus, it is possible to advance
the hypothesis that CCK may be included in that group of
medullary-synthesized regulatory peptides (13) that are
involved in the paracrine fine-tuning of aldosterone secretion.
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Footnotes
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Abbreviations: Ang-II, Angiotensin II; CCK, cholecystokinin;
CCK1-R, cholecystokinin receptor 1; GAPDH, glyceraldehyde-3-phosphate
dehydrogenase; ZF/R, zona fasciculata-reticularis; ZG, zona
glomerulosa.
Received March 5, 2001.
Accepted for publication May 5, 2001.
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References
|
|---|
-
Crawley JN, Corwin RL 1994 Biological actions
of cholecystokinin. Peptides 15:731–755[CrossRef][Medline]
-
Noble F, Wank SA, Crawley JN, et al. 1999 International union of pharmacology. XXI. Structure, distribution, and
functions of cholecystokinin receptors. Pharmacol Rev 51:745–781[Abstract/Free Full Text]
-
Sander LD, Porter JR 1988 Influence of bombesin,
CCK, secretin and CRF on corticosterone concentration in the rat.
Peptides 9:316–320
-
Parrot RF, Ebenezer IS, Baldwin BA, Forsling ML 1991 Central and peripheral doses of cholecystokinin that inhibit
feeding in pigs also stimulate vasopressin and cortisol release. Exp
Physiol 76:625–631
-
Kamilaris TC, Johnson EO, Calogero AE, et al. 1992 Cholecystokininoctapeptide stimulates
hypothalamic-pituitary-adrenal function in rats: role of
corticotropin-releasing hormone. Endocrinology 130:1764–1774[Abstract]
-
Katsuura G, Ibii N, Matsushita A 1992 Activation
of CCK-A receptors induces elevation of plasma corticosterone in rats.
Peptides 13:203–205[CrossRef][Medline]
-
Ebenezer IS, Parrott RF 1996 The effects of
central administration of the CCK-B receptor agonist pentagastrin on
feeding and cortisol release in sheep. Methods Find Exp Clin Pharmacol 18:235–238[Medline]
-
Malendowicz LK, Jedrzejczak N, Macchi C, et al. 1998 Effects of cholecystokinin on the pituitary-adrenal axis of rats
with intact and regenerating adrenal glands. Biomed Res 19:303–308
-
Abelson JL, Liberzon I 1999 Dose response of
adrenocorticotropin and cortisol to the CCK-B agonist pentagastrin.
Neuropsychopharmacology 21:485–494[CrossRef][Medline]
-
Heym C 1997 Immunocytochemical correlates of an
extrapituitary adrenocortical regulation in man. Histol Histopathol 12:567–581[Medline]
-
Aarnisalo AM, Vainio PJ, Mannisto PT, Vasar E, Tuominen
RK 1996 Evidence for cholecystokinin A receptors in bovine adrenal
chromaffin cells. NeuroReport 7:2167–2170[Medline]
-
Nussdorfer GG 1996 Paracrine control of adrenal
cortical function by medullary chromaffin cells. Pharmacol Rev 48:495–530[Medline]
-
Porter JR, Sander LD 1981 The effect of
cholecystokinin octapeptide on pituitary-adrenal hormone secretion.
Regul Pept 2:245–252[CrossRef][Medline]
-
Andreis PG, Markowska A, Champion HC, Mazzocchi G,
Malendowicz LK, Nussdorfer GG 2000 Adrenomedullin enhances cell
proliferation and deoxyribonucleic acid synthesis in rat adrenal zona
glomerulosa: receptor subtype involved and signaling mechanism.
Endocrinology 141:2098–2104[Abstract/Free Full Text]
-
Mazzocchi G, Rossi GP, Neri G, Malendowicz LK, Albertin
G, Nussdorfer GG 1998 11ß-Hydroxysteroid dehydrogenase
expression and activity in the human adrenal cortex. FASEB J 12:1533–1539[Abstract/Free Full Text]
-
Wank SA, Harkins R, Jensen RT, Shapira H, de Weerth A,
Slattery T 1992 Purification, molecular cloning, and functional
expression of the cholecystokinin receptor from rat pancreas. Proc Natl
Acad Sci USA 89:3125–3129[Abstract/Free Full Text]
-
Wank SA, Pisegna JR, de Weerth A 1992 Brain and
gastrointestinal cholecystokinin receptor family: structure and
functional expression. Proc Natl Acad Sci USA 89:8691–8695[Abstract/Free Full Text]
-
Funakoshi A, Miyasaka K, Kanai S, et al. 1996 Pancreatic endocrine dysfunction in rats not expressing the
cholecystokinin-A receptor. Pancreas 12:230–236[Medline]
-
Tso JY, Sun XH, Kao TH, Reece KS, Wu R 1985 Isolation and characterization of rat and human
glyceraldehyde-3-phosphate cDNAs: genomic complexity and molecular
evolution of the gene. Nucleic Acids Res 13:2485–2502[Abstract/Free Full Text]
-
Belloni AS, Rossi GP, Andreis PG, et al. 1996 Endothelin adrenocortical secretagogue effect is mediated by the B
receptor in rats. Hypertension 27:1153–1159[Abstract/Free Full Text]
-
Neri G, Malendowicz LK, Andreis PG, Nussdorfer GG 1993 Thyrotropin-releasing hormone inhibits glucocorticoid secretion of
rat adrenal cortex: in vivo and in vitro studies.
Endocrinology 133:511–514[Abstract]
-
Malendowicz LK, Nussdorfer GG, Nowak KW, Mazzocchi
G 1994 The possible involvement of galanin in the modulation of
the function of rat pituitary-adrenocortical axis under basal and
stressful conditions. Endocr Res 20:307–317[Medline]
-
Vinson GP, Whitehouse BJ, Hinson JP 1992 The
adrenal cortex. Englewood Cliffs: Prentice Hall; 65–139
-
Gaumann DM, Yaksh TL 1988 Adrenal and intestinal
secretion of catecholamines and neuropeptides during splanchnic artery
occlusion shock. Circ Shock 26:391–407[Medline]
-
Gaumann DM, Yaksh TL 1988 Effects of hemorrhage and
opiate antagonists on adrenal release of neuropeptides in cats.
Peptides 9:393–405[CrossRef][Medline]
-
Bardram L, Hilsted L, Rehfeld JF 1989 Cholecystokinin, gastrin and their precursors in pheochromocytomas.
Acta Endocrinol (Copenh) 120:479–484[Medline]
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89(3):
1277 - 1284.
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Abstract
Introduction
