Effects of proglumide on pancreatic acinar cell function

Proglumide, a putative gastrin receptor antagonist, inhibited cholecystokinin (CCK)-stimulated amylase release and [3H]-2-deoxy-D-glucose uptake by isolated mouse pancreatic acini. Inhibition was reversible and competitive in nature with a KI of 0.7 mM. Proglumide also competitively inhibited the binding of 125I-CCK to its receptor in pancreas and brain; the KI for this interaction was 1.0 mM. In contrast, proglumide did not inhibit carbachol-stimulated amylase release, insulin-stimulated glucose transport and protein synthesis, or the binding of insulin to its receptors. Proglumide at 10 mM did, however, reduce both basal [3H]-2-deoxy-D-glucose uptake and [3H]-leucine incorporation into protein. We conclude that proglumide is a competitive and specific, albeit weak antagonist of CCK receptors. Higher concentrations of the drug may have other more nonspecific effects.     

Effects of a new proglumide analogue CR 1392 on pancreatic exocrine secretion in the rat

The effects of proglumide analogue. CR 1392, on pancreatic exocrine secretion were studied in the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, CR 1392 caused a parallel rightward shift of the dose-response curve for amylase secretion stimulated by cholecystokinin octapeptide (CCK-8). CR 1392 inhibited maximally stimulated amylase release by CCK-8 (100 pM) in a concentration-dependent manner, with a half maximal inhibition (ID50) at 8.0 +/- 0.6 microM. CR 1409, another proglumide analogue, also caused a concentration-dependent inhibition (ID50: 3.2 +/- 0.4 microM). Although CR 1409 was about 2.5-fold more potent than CR 1392 in inhibiting the stimulated amylase release, 1 mM CR 1409 caused 107.4 +/- 0.9% increase in amylase release, suggesting acinar cell damage. CR 1392 (1 mM) also caused 19.9 +/- 2.3% increase in amylase release, but was less toxic than CR 1409. The antagonism produced by CR 1392 was selective for CCK and had no effect on amylase release stimulated by other receptor secretagogues or by agents bypassing receptors. CR 1392 added 20 min after the CCK-8 stimulation rapidly abolished pancreatic exocrine secretion in both isolated acini and isolated perfused pancreas. Although the inhibitory effect of CR 1392 was fully reversible in the isolated acini, the pancreata perfused with 100 microM CR 1392 for 20 min did not respond to the subsequent stimulation with CCK-8 for more than 20 min. These results indicate that CR 1392 is a potent, competitive, specific and long acting antagonist of CCK in rat pancreas.     

Effect of antigastrin (SC-15396) on amylase release and 2-deoxyglucose uptake in mouse pancreatic acini

The effects of antigastrin (SC-15396) on amylase release and 2-deoxyglucose uptake were studied in dispersed acini from mouse pancreas. Antigastrin at concentrations between 0.5 and 2 mM inhibited cholecystokinin (CCK)-stimulated amylase release and 2-deoxyglucose uptake in a dose-dependent fashion. Antigastrin at concentrations between 0.5 and 2 mM inhibited carbachol-stimulated amylase release and 2-deoxyglucose uptake as well. In addition, the drug (2 mM) inhibited bombesin-stimulated amylase release and 2-deoxyglucose uptake. In contrast, the stimulation of amylase release by Ca2+ ionophore A23187 was not inhibited by antigastrin. The results, therefore, suggest that antigastrin nonselectively inhibits the actions of these secretagogues probably at their receptor sites.     

Effects of porcine gastrin-releasing peptide on amylase release, 2-deoxyglucose uptake, and alpha-aminoisobutyric acid uptake in mouse pancreatic acini

The effects of synthetic porcine gastrin-releasing peptide (pGRP), a recently isolated gut hormone, were studied in isolated mouse pancreatic acini. pGRP was found to exert direct effects on amylase release, 2-deoxyglucose ( [3H] 2DG) uptake, and alpha-aminoisobutyric acid (AIB) uptake. The stimulatory effect of pGRP on amylase release was significant at 100 pM, and maximal at 1 nM. Higher concentrations of pGRP exerted a smaller stimulatory effect on amylase release. pGRP also increased [3H]2DG uptake, exerting a detectable effect at 300 pM, and a maximal effect at 30 nM. In contrast to its stimulatory effect on amylase release and [3H]2DG uptake, pGRP inhibited AIB uptake. A significant inhibitory effect on AIB uptake occurred at 100 pM, and a maximal inhibitory effect occurred at 3 nM. Dose-response curves of pGRP for amylase release and AIB uptake were found to be biphasic. Bombesin was also found to stimulate amylase release with a biphasic dose-response curve in mouse acini. Both cholecystokinin (CCK) octapeptide and the cholinergic analog carbachol exerted similar effects in isolated mouse acini. However, the effects of pGRP were not inhibited by either dibutyryl cyclic guanosine 3',5'-monophosphate or atropine, whereas the effects of CCK octapeptide were inhibited by dibutyryl cyclic guanosine 3',5'-monophosphate and the effects of carbachol were inhibited by atropine. These results indicate that pGRP can mimic the biological effects of CCK and acetylcholine, but that its actions are probably mediated via a separate class of receptors in mouse acini.     

Effect of ursodeoxycholate on pancreatic exocrine secretion in vitro and in vivo study]

In the present study, we examined the effect of ursodeoxycholate (UDCA) and it's taurine conjugate (TUDC) on rat pancreatic exocrine secretion using dispersed pancreatic acini (in vitro) and conscious rats (in vivo). In in vitro study 300 microM UDCA significantly increased 10(-12)-10(-9) M CCK-8 stimulated amylase release and change of intracellular Ca2+ concentration, but TUDC did not have these effects. In in vivo study intraduodenal infusion of UDCA but not TUDC stimulated pancreatic exocrine secretion. Intravenous infusion of secretin antibody decreased bicarbonate output, however, this increase was not prevented by CCK antagonist. Thus, it was suggested that UDCA has direct action on pancreatic acini and UDCA infused intraduodenally stimulates pancreatic secretion, possibly via the release of a secretin-like substance. The taurine conjugate has weak bioactivity on pancreatic exocrine secretion in both in vitro and in vivo.     

Effect of pancreastatin on pancreatic endocrine and exocrine secretion

Pancreastatin is a novel peptide that was recently purified from extracts of the porcine pancreas. The present study shows that pancreastatin (10(-9)-10(-8) M) can stimulate release of insulin from both the isolated perfused rat pancreas and from cultured rat islet cells in the presence of a low, non-insulinotropic concentration of glucose (4.2 mM). Pancreastatin (10(-9) M) can also inhibit release of insulin stimulated by a high concentration of glucose (16.7 mM). Pancreastatin, at 10(-8) M, can enhance glucose (8.3 mM) induced release of insulin in the static islet cell incubation. In addition, pancreastatin (10(-9)-10(-8) M) can inhibit, in a dose-dependent fashion, cholecystokinin (CCK)-8 stimulated release of amylase from dispersed guinea pig pancreatic acini. Pancreastatin alone, however, did not affect basal release of amylase. Our study shows that pancreastatin can exert a direct effect on both pancreatic endocrine and exocrine secretion.     

Proglumide and benzotript: members of a different class of cholecystokinin receptor antagonists.

In dispersed acini from guinea pig pancreas, proglumide (DL-4-benzamido-N, N-dipropylglutaramic acid) and benzotript (N-p-chlorobenzoyl-L-tryptophan) caused a rightward shift in the dose--response curve for cholecystokinin-stimulated amylase secretion but did not alter the maximal increase in amylase secretion caused by cholecystokinin. At relatively low concentrations, proglumide did not alter the stimulation of enzyme secretion caused by secretagogues whose effects are mediated by adenosine 3'5'-monophosphate (e.g., vasoactive intestinal peptide or secretin) and did not alter the stimulation of enzyme secretion caused by secretagogues that have a mode of action similar to that of cholecystokinin but act through different receptors (e.g., bombesin, physalaemin, eledoisin, and ionophore A23187). There was a close correlation between the ability of proglumide or benzotript to inhibit binding of 125I-labeled cholecystokinin to its receptors on pancreatic acini and the abilities of these compounds to inhibit the action of cholecystokinin on enzyme secretion and on calcium outflux. These results indicate that proglumide and benzotript are members of a different class of cholecystokinin receptor antagonists.     

Inhibitory effect of a new proglumide derivative, loxiglumide, on CCK action in isolated rat pancreatic acini

The effect of a new proglumide derivative, loxiglumide (DL-4-(3,4-dichloro-benzoyl-amino)-5-(N-3-methoxy-propyl-pentylamino+ ++)-5-oxo-pentanic acid; CR 1505), on binding of 125I-CCK-8 and amylase release stimulated by CCK-8 was investigated in isolated rat pancreatic acini. Loxiglumide inhibited CCK-8-stimulated amylase release and binding of 125I-CCK-8 to rat pancreatic acini in a dose-dependent manner. Loxiglumide caused a concentration-dependent rightward shift of the dose-response curve for CCK-8-stimulated amylase release without altering the maximal response. Schild plots showed a slope of 0.82 and pA2 value of 7.05. The inhibitory effect of loxiglumide on amylase release was reversible. Loxiglumide significantly inhibited amylase release in response to CCK-8, caerulein and gastrin-I. However, loxiglumide had no effect on amylase release stimulated by other receptor secretagogues (bombesin, carbamylcholine, secretion and vasoactive intestinal polypeptide) or by agents bypassing receptors (A23187 and TPA). These results indicate that loxiglumide acts as a potent, competitive and specific CCK antagonist on the pancreatic acini.     

Disruption of cholecystokinin (CCK)-B receptor gene did not modify bile or pancreatic secretion or pancreatic growth: a study in CCK-B receptor gene knockout mice.

Pancreatic exocrine function and bile secretion were examined in cholecystokinin (CCK)-B receptor gene-targeted mice and compared among different genotypes [i.e., CCK-B receptor gene: (+/+), wild-type; (+/-), heterozygous; and (-/-), homozygous deficient]. The histology and protein concentrations in the pancreas also were examined. Amylase release from the dispersed acini was examined in vitro by using the various doses of CCK-8, carbachol, and secretin. In vivo, the bile and pancreatic juice were collected, and the concentrations of amylase and bile acid were measured in anesthetized mice. The responses to CCK (100 pmol/kg) or acetyl-beta-methylcholine (500 nmol/kg) were examined. In vitro studies showed that the maximal effective concentrations of CCK-8 (10(-l0) M), carbachol (10(-5) M), and secretin (5 x 10(-7) M) were comparable for all genotypes. Fluid, amylase, and bile acid outputs in vivo also were comparable for all genotypes. Pancreatic wet weight and protein concentrations were not significantly different, and no abnormal findings were observed on histologic examination in any genotype. These results indicated that the CCK-B receptor has no role in pancreatic growth, exocrine secretion, or bile secretion in adult mice.     

Distribution, release, and secretory activity of epidermal growth factor in the pancreas.

This study was designed to determine the distribution of immunoreactive epidermal growth factor (EGF) in the gastrointestinal tract and the action of this peptide on pancreatic secretion in vivo and in vitro. Immunoreactive EGF was found in large amounts in the salivary glands and the pancreas and in the pancreatic juice. EGF infused subcutaneously (50 micrograms/kg-h) in conscious rats with intact or removed salivary glands stimulated pancreatic protein secretion after 4 h of peptide infusion; this effect was completely prevented by the pretreatment with DL-difluoromethyl-ornithine (DFMO) (200 mg/kg), an irreversible inhibitor of activity of ornithine decarboxylase (ODC), a key enzyme in polyamine synthesis. EGF added to the incubation medium in concentrations ranging from 10(-10)-10(-6) M increased, in a concentration-dependent manner both unstimulated and stimulated by caeruelin or urecholine, amylase release from dispersed pancreatic acini obtained from rats pretreated in 3 h with EGF in a dose of 50 micrograms/kg-h. Spermine given at concentrations ranging from 10(-12)-10(-6) M to the freshly prepared rat pancreatic acini also increased amylase release in a concentration-related manner. DFMO injected in a single dose (200 mg/kg), before the infusion of EGF to the rats, completely abolished the stimulatory effect of EGF on amylase release, but failed to affect that of spermine. This study shows that 1. EGF is present in large amounts in pancreatic tissue and pancreatic juice. 2. EGF stimulates pancreatic secretion in vivo and amylase release in vitro from isolated rat pancreatic acini. 3. The activation of ODC and polyamine biosynthesis in acinar cells plays an important role in EGF-induced stimulation of pancreatic secretion.     

CR-1409: a potent inhibitor of cholecystokinin-stimulated amylase release and cholecystokinin binding in rat pancreatic acini

The effects of a new glutaramic acid derivative, 3,4-dichloro-benzamido-N, N-dipentyl-glutaramic acid (CR-1409), on cholecystokinin-stimulated amylase release and 125I-cholecystokinin octapeptide binding were studied in isolated rat pancreatic acini. CR-1409 at concentrations between 0.3 and 30 microM inhibited cholecystokinin-stimulated amylase release in a dose-dependent manner without appreciable effect on the basal amylase secretion. Biphasic dose-response curves to cholecystokinin for amylase release shifted to the right with an increase in the concentration of the drug. IC50 (half-maximal inhibitory concentration) of CR-1409 for cholecystokinin-stimulated amylase release was 0.64 microM, and the potency of this drug on the inhibition of amylase release was 3400 times greater than that of proglumide. The effect of CR-1409 was rapid, reversible, and selective for cholecystokinin. In addition, CR-1409 at concentrations between 0.1 and 30 microM inhibited 125I-cholecystokinin octapeptide binding to rat pancreatic acini. IC50 of CR-1409 for 125I-cholecystokinin octapeptide binding was 0.22 microM, and the potency of this drug on the effect was 5900 times greater than that of proglumide.     

Role of CCK-A receptor for pancreatic function in mice: a study in CCK-A receptor knockout mice

INTRODUCTION: The cholecystokinin (CCK) family of peptides and receptors is present throughout the brain and gastrointestinal tract. The CCK receptors can be pharmacologically subdivided into two subtypes: CCK-A and CCK-B. CCK-A receptor is enriched in the pancreas of mice. AIMS: To determine pancreatic functions in a CCK-A receptor deficient mouse mutant generated by gene targeting in embryonic stem cells. The targeting vector contained lacZ and neo insertions in exon 2. METHODOLOGY: To examine exocrine functions, amylase release from the dispersed acini in vitro was examined. In the in vivo study, the mixture of bile-pancreatic juice was collected, and amylase, bicarbonate, and bile acid outputs were determined after the administration of various stimulants. The cystic duct of the gallbladder and the pylorus were ligated to exclude the involvement of gallbladder contraction and gastric acid. Pancreatic enzyme content was measured, and histologic examinations by HE and lacZ staining were conducted. To examine endocrine functions, oral glucose tolerance test (2 g/kg) was determined. RESULTS: The body weight, pancreatic wet weight, and enzyme content in the pancreas were similar among the three genotypes. Amylase release in vivo and in vitro and bicarbonate secretion in vivo were not stimulated by CCK-8 in CCK-AR (-/-) mice, whereas the responses to other stimulants were substantial in (-/-) mice. Administration of secretin did not increase bicarbonate secretion regardless of genotype. A normal glucose tolerance was observed in (-/-) mice. Acinar cells, islets, and duct cells were stained by lacZ, and HE staining revealed no pathologic findings. CONCLUSION: The CCK-A receptor is important for pancreatic exocrine secretion, but not essential for maintaining glucose concentration and pancreatic growth in mice.     

Oxyntomodulin inhibits pancreatic secretion through the nervous system in rats

Glicentin (GLIC), oxyntomodulin (OXM), and peptide YY (PYY) released in blood by ileocolonic L-cells after meals may inhibit pancreatic secretion. Whereas OXM interacts with glucagon and tGLP-1 receptors, OXM 19-37, a biologically active fragment, does not. The purpose of this study was to measure the effect of OXM, OXM 19-37, GLIC, tGLP-1, and PYY on pancreatic secretion stimulated by 2 deoxyglucose (2DG), electrical stimulation of the vagus nerves (VES), acetylcholine and cholecystokinin octapeptide (CCK8) in anesthetized rats. The effect of OXM was also studied in dispersed pancreatic acini. Plasma oxyntomodulin-like immunoreactivity (OLI) was measured by radioimmunoassay after the exogenous infusion of OXM and after an intraduodenal meal. OXM 19-37, infused at doses mimicking postprandial plasma levels of OLI, decreased pancreatic secretion stimulated by 2DG, VES, or CCK8. Similar effects were found with OXM and GLIC. OXM 19-37 did not change the pancreatic stimulation induced by acetylcholine in vivo, or CCK-induced amylase release in isolated acini. Vagotomy completely suppressed the inhibitory effect of OXM 19-37 on CCK8-stimulated pancreatic secretion. PYY inhibited the effect of 2DG, but not that of CCK8, whereas tGLP-1, even in pharmacologic doses, had no effect on stimulated pancreatic secretion. OXM, OXM 19-37, but not tGLP-1, inhibit pancreatic secretion at physiologic doses, through a vagal neural indirect mechanism, different from that used by PYY, and probably through a GLIC-related peptide-specific receptor.     

Loxiglumide

D,l-4-(3,4-dichlorobenzoylamino)-5-(N-3-methoxypropyl-pentylamino)-5-oxopentanoic acid (CR 1505; loxiglumide) is a newly developed analog of proglumide. We examined the inhibitory effects of loxiglumide on pancreatic exocrine function in the isolated pancreatic acini and the isolated perfused pancreata of rats. Loxiglumide inhibited cholecystokinin octapeptide (CCK-8)-stimulated amylase release and, similarly, binding of[ ¹²⁵ I]CCK-8 to isolated rat pancreatic acini. Loxiglumide was about 3000 times more potent than the reference substance proglumide, but was about 1000 times less potent than L-364,718, another new CCK antagonist having benzodiazepine ring, in inhibiting CCK-8-stimulated amylase release. The inhibitory effect of loxiglumide displayed competitive kinetics and was specific for CCK in that the effects of other receptor secretagogues or agents bypassing receptors were not altered. The inhibitory effect of loxiglumide was fully reversible in isolated acini. However, the pancreata perfused with 10 M loxiglumide for 20 min did not respond to CCK-8 for more than 20 min even after the removal of loxiglumide infusion. In contrast, an immediate increase in pancreatic exocrine secretion was observed after proglumide removal. Loxiglumide appeared to be bound to the receptors on acinar cells in a slowly dissociating state. These results indicate that loxiglumide acts as a potent, competitive, and specific CCK antagonist on the exocrine pancreas and, because of its prolonged inhibitory action, may be useful as a therapeutic agent in pancreatic disease.This work was supported in part by a grant from the Japanese Ministry of Health and Welfare (Intractable Diseases of the Pancreas).     

Bioactivity of synthetic human cholecystokinin (CCK)-33 in vitro and in vivo.

The relative potencies of synthetic human cholecystokinin (h-CCK)-33, porcine CCK-33 (p-CCK-33) and CCK-8 were examined by measuring pancreatic secretion in the conscious rat (in vivo) and amylase release from rat pancreatic acini using a perifusion study (in vitro). The increments of protein output during an 1-hr infusion of 100 pmol/kg/hr of h-CCK-33, p-CCK-33 and CCK-8 were 27.0 +/- 2.9 mg/hr (M +/- SE), 19.3 +/- 2.8 and 14.0 +/- 1.8 mg/hr, respectively. H-CCK-33 and p-CCK-33 showed significantly higher responses of protein output than CCK-8 in a same molar ratio, in vivo. In vitro, the stimulation with 10(-10) M h-CCK-33, p-CCK-33 and CCK-8 led to a similar biphasic amylase release in a perifusion study. Twenty-five microM CR-1409, an antagonist for CCK receptor, completely inhibited the 10(-10) M h-CCK-33-stimulated amylase release. Although it was found that h-CCK-33 and p-CCK-33 were more potent than CCK-8 in vivo, 10(-10) M CCK-8, h-CCK-33 and p-CCK-33 were equipotent on rat pancreatic acini in vitro. It is suggested that the discrepancy in potencies of the large molecular form and small molecular form of CCK in vivo and in vitro may be attributed to the delay of degradation of the large molecular form of CCK in vivo.     

Action of secretagogues on amylase release from dog pancreatic acini

This work describes a new preparation of dog pancreatic acini which were used to study amylase release in response to various secretagogues. Neither secretin nor vasoactive intestinal peptide stimulated amylase release from acini. Caerulein, carbachol and human synthetic gastrin G17 stimulated amylase release with the same efficacy, but with different potencies. Bombesin nonapeptide did not show any evidence of a direct stimulatory effect on amylase release. These species-related peculiarities stress the necessity of using the same species when comparing pancreatic cell behaviour in vivo and in vitro.     

Effects of verapamil on amylase release from rat pancreatic acini and its relation to calcium fluxes

The effects of verapamil on amylase release and Ca2+ fluxes from rat pancreatic acini have been studied. Verapamil at concentrations above 10 microM dose-dependently inhibited amylase release stimulated by carbachol, but enhanced the amylase release stimulated by cholecystokinin (CCK) and secretin. Verapamil had no significant effect on calcium uptake induced by carbachol or CCK, but significantly inhibited Ca+2 efflux caused by carbachol and slightly increased that caused by CCK. In a Ca2+-free, EDTA-containing medium, the increase in cytoplasmic free Ca2+ caused by carbachol was significantly inhibited by verapamil. Verapamil alone up to 400 microM had no effect on the release of lactic dehydrogenase. In conclusion, the effect of verapamil on amylase release from rat pancreatic acini differs depending on the type of secretagogue used to stimulate amylase release. This effect is not related to blockage of Ca2+ uptake, indicating another mechanism of verapamil on pancreatic acini.     

The site of action of neurotensin in the rat pancreas.

The tridecapeptide neurotensin, present in endocrine cells of the ileal mucosa and in nerve bodies of cerebral nuclei, may play a role in the physiology of exocrine pancreatic regulation. This assumption is based on two observations: Neurotensin appears in the blood stream after a fatty meal and neurotensin stimulates exocrine pancreatic secretion. There has, however, been controversy on the site of action of this peptide since some investigators did not observe an effect on the pancreas in vitro and suggested, therefore, an indirect, perhaps neural or even central site of action. In the present investigation, we compared the action of neurotensin on the exocrine pancreas in vivo in the anesthetized rat after intracerebroventricular (i.c.v.) injection and after i.v. infusion and in vitro after incubation of the pancreas in three different preparations: isolated dispersed acini, isolated lobuli, and isolated total pancreas. We found that i.c.v. application of neurotensin stimulated exocrine pancreatic secretion only when doses were applied that led to elevated peripheral plasma neurotensin levels. In vitro, the action of neurotensin was very weak and the optimal dose was integrity dependent; e.g., a concentration of 10(-4) and 10(-5) M neurotensin was necessary to stimulate amylase release from isolated acini, 10(-8) M neurotensin induced amylase release from isolates lobuli, and 10(-9) M neurotensin released amylase from the intact pancreas. Intravenously, neurotensin resulted in a greater amylase release over basal than in any of the in vitro experiments. We conclude that neurotensin acts directly on the pancreatic acini but that the sensitivity of the pancreas is greatly enhanced when the organ is intact and has normal neural and vascular communications.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of somatostatin on cholecystokinin-induced amylase release in rat pancreatic acini.

The effect of somatostatin on cholecystokinin-induced amylase release was investigated in isolated rat pancreatic acini. Acini were isolated by enzymatic digestion and incubated in a HEPES buffered Ringer's solution with testing reagents for 30 minutes at 37 degrees C. The activity of released amylase, cAMP, and inositol phosphate formation were measured. Intracellular calcium concentration ([Ca2+]i) was also checked. Somatostatin 14 and octreotide, a somatostatin analog, inhibited CCK-stimulated amylase release in a concentration-dependent manner. The inhibitory effect of octreotide on CCK-induced amylase release was not shown when the acini were treated with 8-Br-cAMP, irrespective of the presence of IBMX. Forskolin potentiated CCK-induced amylase release and this effect was blocked by octreotide treatment; although CCK-8 (3 x 10(-11) M) failed to stimulate cAMP formation, octreotide significantly inhibited basal cAMP formation in the acini. The increase of [Ca2+]i in response to CCK was inhibited by octreotide. However, CCK-induced inositol phosphate formation was not changed by 10(-9) M octreotide. Octreotide had no effect on CCK-stimulated tyrosine phosphorylation, and tyrosine phosphatase inhibitors (NaF and Na2WO4) did not influence the effect of octreotide on CCK-induced amylase release. From these results, we conclude that octreotide inhibits CCK-induced amylase release by inhibiting basal cAMP formation and decreasing the [Ca2+]i stimulated by CCK.     

Effect of somatostatin on pancreatic enzyme secretion

The effect of somatostatin (SS) on the pancreatic enzyme secretion was studied in a perfusion system using dispersed pancreatic rat acini in vitro. In addition the effect of SS on pancreatic secretion in vivo was also studied in conscious rats for comparison. In an in vitro study, 6×10^-7M SS-14 caused no significant change in amylase release when added 20 min before stimulation by 10^-5M carbamylcholine (Cch), 10^-6M A23187, 5×10^-7M secretin and 2mM dibutyryl cyclic AMP. The addition of 6×10^-7M SS-28 also caused no significant change in amylase release stimulated by 10^-5M Cch. High performance liquid chromatographic examination indicated that no degradation of either SS-14 or SS-28 occurred after reaction with dispersed acini. In an in vivo study SS-14 caused marked inhibition of basal pancreatic secretion and stimulated pancreatic secretion by bile-pancreatic juice diversion. These results indicate that SS has no direct inhibitory action on rat pancreatic secretion, and that SS may inhibit the pancreatic secretion by indirect mechanisms.