Search PubMed⌕ Search

Biomedical subjects

W E Schmidt

Publications and source records attributed to W E Schmidt.

At least 109 records · Page 6Linked to original sources
PubMed1994

Structure/activity characterization of glucagon-like peptide-1.

Glucagon-like peptide-1 is a gastrointestinal hormone that strongly stimulates insulin release via specific receptors on the pancreatic beta-cell. To characterize the side-chain groups required for interaction of glucagon-like peptide-1 with its receptor, we performed binding studies with alanine-substituted glucagon-like peptide-1 analogues on RINm5F insulinoma cells. The binding affinity and biological activity of glucagon-like peptide-1 have been found to be sensitive to alanine exchanges in the N-terminal positions 1, 4, 6 and the C-terminal positions 22 and 23. Alanine substitutions at positions 5, 8, 10-12, 14, 16-21 and 25-30 do not change receptor affinity. These findings could be exploited to design glucagon-like peptide-1 agonists and probably antagonists for further physiological studies.

Amino Acid Sequence↗
PubMed1994

Calyculin A, okadaic acid and W-7 interfere with a distal step in pancreatic acinar signal transduction.

The effects of the serine/threonine phosphatase inhibitors calyculin A, okadaic acid and the calmodulin antagonist W-7 on amylase secretion were studied in pancreatic acini. Calyculin A and okadaic acid dose-dependently inhibited amylase secretion to basal levels when stimulated with the intracellularly acting secretagogues thapsigargin, 8-br-cAMP or PMA. W-7 dose-dependently inhibited thapsigargin- or 8-br-cAMP-induced amylase secretion. In combination, thapsigargin, 8-br-cAMP and PMA induced amylase secretion comparable to the stimulation by cholecystokinin. Their effect was significantly inhibited by calyculin A, okadaic acid or W-7. These data imply that type 1- and 2b-phosphatases and calmodulin play a key role in the stimulation of exocrine pancreatic secretion at a distal step of both the Ca2+/IP3- and cAMP-mediated signal-transduction pathways.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Gastrin-releasing peptide and CCK after intraduodenal inhibition of proteases in dogs.

The intraduodenal application of a potent protease inhibitor (camostate, 600 mg) causes a significant increase in basal pancreatic secretion in the manner of a negative-feedback mechanism. The integrated protein secretion during the entire study period was 9.9 +/- 1.8 g in 120 min. The iv application of anti-GRP immunoglobulin caused a significant reduction to 5.0 +/- g in 120 min. No significant changes in the plasma concentrations of GRP and CCK were detectable. The increased secretion occurring after the administration of the protease inhibitor could be mediated by neural GRP-dependent mechanisms. These may also be relevant for CCK-dependent factors, which are only briefly mentioned.

Animals↗
PubMed1994

Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans.

BACKGROUND/AIMS: The role of cholecystokinin (CCK) in the regulation of gastric acid secretion is still controversial. This study examined the effect of the CCK-A receptor antagonist loxiglumide (lox) on gastrin- or CCK-induced gastric acid secretion and meal-stimulated plasma gastrin levels in a placebo-controlled study. METHODS: Acid output was studied in eight subjects who received intravenously gastrin-17 (15, 30, and 60 pmol.kg-1.h-1); gastrin-17 plus lox; cholecystokinin octapeptide (CCK-8) (15, 30, and 60 pmol.kg-1.h-1); CCK-8 plus lox; or gastrin plus CCK-8. Sham feeding-induced acid output and meal-stimulated gastrin secretion were studied during lox infusion. RESULTS: Gastrin-17 dose-dependently stimulated acid output to near-maximal levels. CCK-8 (15 pmol.kg-1.h-1) increased acid secretion 2.5-fold over basal; higher infusion rates had less or no effect. When combined with lox, CCK-8 produced a near-maximal acid response (6-fold over basal). CCK-8 together with gastrin-17 inhibited gastrin-induced acid output by 67%. Meal-stimulated plasma gastrin concentrations were elevated 3.2-fold, whereas sham feeding-induced acid secretion was not modified by lox. CONCLUSIONS: Blockade of CCK-A receptors converts CCK-8 into a potent acid secretagogue and augments postprandial gastrin secretion. A CCK-mediated stimulation of paracrine somatostatin secretion from antral and fundic D cells represents a candidate mechanism for the inhibition of the parietal and gastrin cell in humans.

Adult↗
PubMed1994

Cyclosporine A inhibits protein-kinase-C-mediated amylase release from isolated rat pancreatic acini.

The present study was performed to characterize a direct influence of cyclosporine A (CsA) on exocrine pancreatic enzyme secretion. CsA inhibited dose-dependently amylase release from isolated rat pancreatic acini in response to carbachol or cholecystokinin octapeptide (CCK-8). A significant reduction in amylase release by 17% was observed at 0.2 mumol/l CsA (p < 0.001) when compared to controls. At 0.2 mmol/l, CsA reduced amylase release in response to both secretagogues by maximally 45%, whereas basal secretion was not affected. CsA had no influence on CCK-8-stimulated increase in intracellular Ca2+ concentrations or amylase release in response to the Ca2+ ionophore A 23187. In contrast, the dose-response curve for amylase secretion induced by the phorbol ester phorbolmyristate-13-acetate was shifted to the right without a reduction of the maximal secretory response. Unexpectedly, vasoactive-intestinal-polypeptide- and secretin-stimulated acinar secretion was not diminished by CsA. In isolated pancreatic lobules exposed to 0.1 mmol/l CsA, amylase release stimulated by cerulein or veratridine was reduced by 26.7 +/- 2 or 28.3 +/- 4%, respectively. CsA had no influence on the displacement of 125I-Bolton-Hunter-labeled CCK-8 from acinar CCK receptors. The ultrastructure of cellular organelles in isolated lobules was not altered after incubation with 0.1 mmol/l CsA for 60 min. Our data suggest that CsA interferes with protein-kinase-C-mediated signal transduction in isolated rat pancreatic acini, without affecting cAMP-dependent signalling.

Amylases↗
PubMed1994

Identification and biochemical characterization of the human brain galanin receptor.

Human galanin (hGal) is an important neuro-modulator present in the brain, gastrointestinal system and the hypothalamo-pituitary axis. A specific receptor for hGal has been identified in various areas in human brain. A single class of high affinity binding sites was found on plasma membranes of the amygdala (Kd 0.23 nM, Bmax 44 fmol/mg), the hypothalamus (Kd 0.20 nM, Bmax 25 fmol/mg) and the cortex cerebri (Kd 0.11 nM, Bmax 8.2 fmol/mg). Other brain areas, i.e. cerebellum, thalamus or pons, expressed binding sites of identical high affinity in lower quantities (Bmax < 3 fmol/mg). Specific binding of 125I-labelled hGal was found to be reversible, time- and temperature-dependent and inhibited by Ca2+, Na+ and K+ ions at a concentration of 5 mM. Non-hydrolysable guanosine nucleotides potently reduced specific binding of 125-I-labelled hGal by more than 80%. Synthetic hGal analogues substituted in the N-terminal region exhibited strongly reduced binding affinity for the hGal receptor. Using 3-[(3-cholamidopropyl) dimethylammonio]-2-hydroxy-1-propanesulphonate, hGal receptors were successfully solubilized from human cortical membranes, exhibiting no significant loss of binding affinity. Affinity cross-linking to 125I-labelled hGal revealed a labelled band of approximately 60 kDa sensitive to unlabelled Gal. This putative hGal receptor is glycosylated since its molecular size was reduced after treatment with endoglycosidase F. Receptors bound to 125I-labelled hGal could be specifically adsorbed to wheat germ agglutinin and ricinus communis agglutinin, suggesting that receptor glycosylation involves N-acetyl glucosamine and galactose respectively.

Agglutinins↗
PubMed1994

Serine/threonine phosphatases play a role in stimulus-secretion coupling in pancreatic acinar cells.

The role of serine/threonine phosphatases in Ca2+/IP3- and cAMP- mediated stimulus-secretion coupling was investigated in isolated pancreatic acinar cells. Cyclosporine A, an inhibitor of type 2b serine/threonine phosphatases, maximally reduced CCK-8-stimulated amylase secretion by 33%. In contrast, the secretory response to secretin or PACAP-(1-27) was not significantly altered by cyclosporine A independent of the secretagogue-concentration okadaic acid significantly reduced amylase release, induced by Ca2+/IP3-mediated- (CCK-8) or cAMP-mediated agonists (secretin, PACAP-(1-27), VIP) at concentrations that primarily inactivate type 1 and 2b phosphatases. Calyculin A, another type 1 and 2a phosphatase inhibitor, had a similar inhibitory effect on CCK-8-, secretin- or PACAP-(1-27)-induced secretion. In permeabilized acini, cyclosporine A reduced calcium-induced amylase release by 20%, whereas okadaic acid and calyculin A had an inhibitory effect by 55% and 52%, respectively. The ultrastructure of CsA-incubated acinar cells was not different from vehicle-incubated control lobules. In contrast, incubation with okadaic acid for 60 min resulted in morphological alterations of the Golgi apparatus, leading to a fragmentation of Golgi cisternae into small vesicles. Our data suggest a role of type 1 and 2b phospatases in stimulus-secretion coupling of both signal-transduction pathways in pancreatic acinar cells. These phosphatases might also be important for the maintenance of pancreatic cellular ultrastructure.

Amylases↗
PubMed1994

Purification of the PACAP-1 receptor by ligand affinity chromatography.

Employing the Fmoc solid phase strategy, analogues of pituitary adenylate cyclase activating polypeptide (PACAP) were synthesized containing single cysteine residues. Monobiotinylation of these analogues was achieved via thioether formation between the sulfhydryl groups provided by the cysteine residues and the biotinylation reagent N-lodoacetyl-N'biotinyl-hexylenediamine. Almost all of the S-biotinylated analogues revealed full binding activity to the solubilized PACAP-1 receptor from pig brain membranes. To minimize sterical hindrance of ternary complex formation between the biotinylated analogues, the PACAP-1 receptor and streptavidin, an analogue was designed which contains seven consecutive alanine residues between position 28 and 34. This biotinylated analogue, S-biotinyl[Ala28-34,Cys35]PACAP(1-35), was highly capable of ternary complex formation and therefore used as high affinity ligand for affinity chromatography. By means of lectin adsorption chromatography and ligand affinity chromatography the PACAP-1 receptor was purified more than 6000-fold from porcine brain membranes solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propane-sulfonate (CHAPSO).

Animals↗
PubMed1994

Inhibitory transmission in tenia coli mediated by distinct vasoactive intestinal peptide and apamin-sensitive pituitary adenylate cyclase activating peptide receptors.

Inhibitory transmission in tenia coli involves both vasoactive intestinal peptide (VIP) and an apamin-sensitive transmitter. The present study examined whether pituitary adenylate cyclase activating peptide (PACAP) is released from tenia coli and accounts for the apamin-sensitive component of neurally mediated relaxation. Electrical field stimulation (0.25-4 Hz) elicited frequency-dependent relaxation and PACAP release; earlier studies had shown a similar pattern for VIP release and an absence of nitric oxide generation in this tissue. A combination of specific PACAP-27 and PACAP-38 monoclonal antibodies (each 100 micrograms/ml), the PACAP antagonist PACAP6-38 and desensitization with PACAP inhibited relaxation induced by all frequencies of stimulation. The magnitude of inhibition elicited by each treatment (38 +/- 3%-41 +/- 3% at 4 Hz) was similar to that elicited by apamin (44 +/- 11%) and was not augmented by apamin. VIP antibody (1:60), the VIP antagonist, VIP10-28 and VIP desensitization also inhibited relaxation (33 +/- 2%-35 +/- 5% at 4 Hz). Inhibition by each treatment was augmented additively by apamin (76 +/- 3%-85 +/- 3%) as well as by combination with PACAP antibody, PACAP antagonist and PACAP desensitization (76 +/- 6%-80 +/- 3%). Measurements in muscle strips and dispersed tenia coil muscle cells showed that VIP10-28 inhibited relaxation induced by VIP only, and PACAP6-38 inhibited relaxation mediated by PACAP-27 or PACAP-38 only, implying interaction of VIP and PACAP with distinct receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Characterization and purification of the solubilized pituitary adenylate-cyclase-activating polypeptide-1 receptor from porcine brain using a biotinylated ligand.

A specific receptor for the brain-gut neuropeptide pituitary adenylate-cyclase-activating polypeptide (PACAP-1 receptor) was solubilized with Chapso from porcine brain plasma membranes and purified. Binding of 125I-PACAP(1-27) to the solubilized material was reversed equipotently by unlabeled PACAP(1-27) and PACAP(1-38). Soluble receptors retained the binding affinities and specificities of the plasma membrane fraction. Scatchard analysis of equilibrium-binding data indicated the existence of a single high-affinity binding site (Kd = 0.23 nM, Bmax = 1.2 pmol/mg protein). Binding of 125I-PACAP(1-27) to solubilized receptors was not affected by guanosine nucleotides, suggesting that solubilization dissociates the PACAP-1 receptor/guanosine-nucleotide-binding protein complex. Affinity cross-linking of 125I-PACAP(1-27) to soluble PACAP-1 receptors identified a specifically labeled 60-kDa protein. Enzymic deglycosylation of soluble affinity-labeled receptors reduced the apparent molecular mass by 10 kDa. The solubilized receptor glycoprotein was purified 4-5-fold by lectin-adsorption chromatography on wheatgerm agglutinin immobilized on agarose. S-Biotinyl[Ala28-34, Cys35]PACAP(1-35) was synthesized, immobilized on streptavidin-coated magnetic Sepharose beads and used to further affinity-purify wheatgerm-agglutinin-eluted receptor material. This more than 6000-fold enriched PACAP-1-receptor-preparation retained single-class high-affinity binding and consisted of an almost homogenous 55-60-kDa protein identified by silver staining. In conclusion, we established a rapid method for purification of PACAP-1 receptors, allowing further studies to be performed by protein chemistry.

Animals↗
PubMed1993

PD 135158, a CCKB/gastrin receptor antagonist, stimulates rat pancreatic enzyme secretion as a CCKA receptor agonist.

The CCKB/gastrin receptor antagonist, PD 135158 (CAM 1028), surprisingly stimulates lipase release from isolated rat pancreatic acini dose dependently in a biphasic manner, with identical efficacy but lower potency compared to cholecystokinin octapeptide (CCK-8). Half-maximal stimulation occurred at 0.6 microM and maximal secretion was induced at 50 microM. Supramaximal concentrations decreased lipase release. Acinar lipase secretion in response to 25 pM CCK-8 or 1 microM CAM-1028 was abolished by 5 microM of the specific CCKA receptor antagonist loxiglumide (CR 1505), half-maximal inhibition was observed at 0.6 microM for CCK-8 and 0.4 microM for PD 135158. These data demonstrate that the CCKB/gastrin receptor antagonist, PD 135158, acts as a full agonist at the rat pancreatic CCKA receptor.

Animals↗
PubMed1993

Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum.

Peptides of the glucagon/vasoactive-intestinal-peptide (VIP) peptide family share a considerable sequence similarity at their N-terminus. They either start with Tyr-Ala, His-Ala or His-Ser which might be in part potential targets for dipeptidyl-peptidase IV, a highly specialized aminopeptidase removing dipeptides only from peptides with N-terminal penultimate proline or alanine. Growth-hormone-releasing factor (1-29)amide and gastric inhibitory peptide/glucose-dependent insulinotropic peptide (GIP) with terminal Tyr-Ala as well as glucagon-like peptide-1(7-36)amide/insulinotropin [GLP-1(7-36)amide] and peptide histidine methionine (PHM) with terminal His-Ala were hydrolysed to their des-Xaa-Ala derivatives by dipeptidyl-peptidase IV purified from human placenta. VIP with terminal His-Ser was not significantly degraded by the peptidase. The kinetics of the hydrolysis of GIP, GLP-1(7-36)amide and PHM were analyzed in detail. For these peptides Km values of 4-34 microM and Vmax values of 0.6-3.8 mumol.min-1.mg protein-1 were determined for the purified peptidase which should allow their enzymic degradation also at physiological, nanomolar concentrations. When human serum was incubated with GIP or GLP-1(7-36)amide the same fragments as with the purified dipeptidyl-peptidase IV, namely the des-Xaa-Ala peptides and Tyr-Ala in the case of GIP or His-Ala in the case of GLP-1(7-36)amide, were identified as the main degradation products of these peptide hormones. Incorporation of inhibitors specific for dipeptidyl-peptidase IV, 1 mM Lys-pyrrolidide or 0.1 mM diprotin A (Ile-Pro-Ile), completely abolished the production of these fragments by serum. It is concluded that dipeptidyl-peptidase IV initiates the metabolism of GIP and GLP-1(7-36)amide in human serum. Since an intact N-terminus is obligate for the biological activity of the members of the glucagon/VIP peptide family [e. g. GIP(3-42) is known to be inactive to release insulin in the presence of glucose as does intact GIP], dipeptidyl-peptidase-IV action inactivates these peptide hormones. The relevance of this finding for their inactivation and their determination by immunoassays is discussed.

Amino Acid Sequence↗
PubMed1993

Role of neurotensin in the regulation of exocrine pancreatic secretion in dogs.

A potential physiological function of the regulatory gastrointestinal peptide neurotensin (NT) is the stimulation of exocrine pancreatic secretion. We investigated therefore whether immunoneutralization of the postprandially circulating peptide, intravenous application of either atropine or the highly specific CCK receptor antagonist, L-364,718, could influence neurotensin-mediated pancreatic secretion in dogs. The use of CCK receptor antagonist (0.1 mg kg-1 intraduodenally) inhibited postprandial and NT-mediated exocrine pancreatic secretion. The integrated postprandial protein secretion fell from 31 +/- 1.6 to 23 +/- 2.1 g 180 min-1 while the corresponding values in response to i.v.-NT (postprandial neurotensin concentration course was imitated by the infusion of 50 pmol kg h-1 NT) fell from 22 +/- 1.9 to 7.5 +/- 0.8 g 180 min-1. Immunoneutralization of postprandial NT led to a simultaneous significant reduction in postprandial pancreatic secretion (integrated protein release 31 +/- 1.6 and 15.5 +/- 1.4 g 180 min-1 respectively). The i.v. application of atropine lowered NT-mediated pancreatic secretion (e.g., protein output) from 22 +/- 1.9 to 7.1 +/- 7.1 +/- 0.9 g 180 min-1. We conclude that NT plays an important role in the endocrine regulation of exocrine pancreatic secretion. This influence could be mediated by a CCK-dependent cholinergic mechanism.

Animals↗
PubMed1993

The influence of bile acids on the regulation of exocrine pancreatic secretion and on the plasma concentrations of neurotensin and CCK in dogs.

The influence of the intestinal bile acid content on the secretion of the exocrine pancreas and on the plasma concentrations of the relevant peptides (NT), and CCK is the subject of continuing controversy. Thus the alterations of pancreatic secretion and both hormones during variations of intestinal bile acid content were investigated. Modified Herrera fistulas were implanted in six dogs for analysis of the pancreatic secretions. Intraduodenal application of taurocholate (1.8, 3.6, or 7.2 mM) led to a marked reduction of the pancreatic secretion as well as to a simultaneous decrease of NT and CCK release after stimulation by the intraduodenal instillation of a 20% lipid emulsion. (The integrated protein secretion decreased from 20.1 +/- 1.9 g to 15.2 +/- 1.6 g, NT release dropped from 4970 to 3050 pg/180 min, and CCK from min.) cholestyramine together with the lipid emulsion had the opposite effect. The pancreatic protein as well as NT and CCK release increased. It therefore appears that there is a negative feedback relationship between the postprandial intestinal bile acid content on the one hand, and the secretion of the exocrine pancreas and the regulatory peptides NT and CCK on the other hand. This relationship is independent of any interaction between pancreatic proteases and bile acids.

Animals↗
PubMed1993

PACAP and VIP stimulate enzyme secretion in rat pancreatic acini via interaction with VIP/PACAP-2 receptors: additive augmentation of CCK/carbachol-induced enzyme release.

The binding and biological effect of pituitary adenylate cyclase activating polypeptide (PACAP), a novel hypothalamic peptide with high sequence homology to vasoactive intestinal polypeptide (VIP), were studied in rat AR 4-2 J pancreatic carcinoma cells and isolated rat pancreatic acini. PACAP(1-27) and analogue PACAP(1-23, VIP-24-28), but not VIP, displaced potently and reversibly 125I-PACAP(1-27) from binding to an abundantly expressed high affinity PACAP-preferring receptor on AR 4-2 J cells, referred to as "PACAP-1 receptor." High affinity binding was dependent on N-terminal and C-terminal residues of PACAP(1-27): PACAP(1-24,Cys-25) (7.3 +/- 1.6 microM), PACAP(1-23) (8.2 +/- 1.5 microM), VIP (> 30 microM), PACAP(3-27), PACAP(1-19), PACAP(3-19), PACAP(1-12), and PACAP(18-38) (all > 50 microM) showed low or no binding potency. In contrast, high and low affinity binding of 125I-VIP to AR 4-2 J cells was displaced equipotently by PACAP(1-27) and VIP, thus defining on these cells, in addition, two scarcely expressed binding sites, designated "VIP/PACAP-2 receptor," similar or identical to the previously described high and low affinity acinar VIP receptor. Binding of 125I-PACAP(1-27) to a high and low affinity binding site on rat pancreatic acini was inhibited equipotently by PACAP(1-27) and VIP, identifying these sites as VIP/PACAP-2 receptors. PACAP(1-23) recognized both type 2 binding sites with only slightly lower affinity. PACAP(1-27), PACAP(1-38), PACAP(1-23, VIP-24-28), and PACAP(1-23) equipotently stimulated acinar lipase release and cyclic AMP production in pancreatic acini. Co-incubation of PACAP(1-27) or VIP with cholecystokinin-8 or carbachol revealed additive effects on enzyme secretion. Our results suggest the predominant expression of VIP/PACAP-2 receptors on rat pancreatic acini, whereas AR 4-2 J cells express mainly PACAP-1 receptors. PACAP is a potent ligand for both receptor types and has to be regarded as a novel VIP-like pancreatic secretagogue.

Amino Acid Sequence↗
PubMed1993

PACAP is a stimulator of neurogenic contraction in guinea pig ileum.

The myotropic effect of pituitary adenylate cyclase-activating polypeptide (PACAP), a novel brain-gut peptide with high sequence homology to vasoactive intestinal polypeptide (VIP), was studied in the isolated guinea pig ileum in vitro. PACAP contracts the guinea pig ileum significantly more potently and efficiently compared with VIP. PACAP-induced contraction was abolished by tetrodotoxin, dynorphin, and somatostatin, partially reduced by atropine, and not affected by ganglionic and adrenergic blockade. The atropine-resistant component was sensitive to spantide, to the induction of tachyphylaxis with substance P, and to omega-conotoxin. Ileal strips desensitized to PACAP did not respond to VIP, although they maintained their sensitivity to PACAP after desensitization to VIP. COOH-terminal-truncated derivatives of PACAP exhibited full biological activity, although some of them showed substantially reduced potency. Deletion of NH2-terminal amino acids abolished biological activity. PACAP produced a concentration-dependent increase in the release of [3H]acetylcholine from longitudinal muscle-myenteric plexus preparations preloaded with [3H]choline. This effect was Ca2+ dependent, tetrodotoxin sensitive, and resistant to hexamethonium and scopolamine. In contrast, PACAP inhibited release of acetylcholine evoked by field stimulation. In summary, PACAP-induced contraction of the guinea pig ileum is mediated via release of acetylcholine and substance P through interaction with PACAP-1 and VIP/PACAP-2 receptors. PACAP has to be added to the list of myotropic neuropeptides of the gastrointestinal tract.

Acetylcholine↗
PubMed1993

Gastrin-releasing peptide and cholecystokinin in the regulation of exocrine pancreatic secretion in dogs.

Exocrine pancreatic secretion in conscious dogs is significantly stimulated by the intravenous application of small doses of gastrin-releasing peptide (GRP; 30 pmol x kg-1 x h-1). There is no increase of the GRP concentrations in peripheral blood which is also the case under physiological postprandial conditions. There is also no increase in the peripheral cholecystokinin (CCK) concentrations, in contrast to previous reports. Nevertheless other CCK-related mechanisms may play an important role, since the administration of the highly specific CCK receptor antagonist MK-329 causes a marked reduction of the GRP-induced exocrine pancreatic secretion.

Animals↗