Effects of galanin on islet cell secretory responses to VIP, GIP, 8-CCK, and glucagon by the perfused rat pancreas

Exogenous galanin has been shown to suppress insulin secretion as elicited by a number of secretagogues such as glucose, arginine, tolbutamide, carbachol, and oral nutrients. To achieve further insight into the influence of galanin on the endocrine pancreas, we have investigated the effect of synthetic porcine galanin (a 200 ng bolus followed by constant infusion at a concentration of 16.8 ng/mL for 16 to 24 minutes) on unstimulated insulin, glucagon, and somatostatin release, as well as on the responses of these hormones to 1 nmol/L vasoactive intestinal peptide (VIP), 1 nmol/L gastric inhibitory peptide (GIP), 1 nmol/L 26 to 33 octapeptide form of cholecystokinin (8-CCK) or 10 nmol/L glucagon in the perfused rat pancreas. Galanin infusion reduced unstimulated insulin secretion by 60% without modifying glucagon and somatostatin output. Galanin also blocked insulin release elicited by VIP, GIP, and 8-CCK, it did not affect the glucagon responses to VIP and GIP, or the somatostatin responses to VIP, GIP, and 8-CCK. Finally, galanin inhibited the insulin output, but not the somatostatin release induced by glucagon. In conclusion, in the perfused rat pancreas, galanin appears to behave as a general inhibitor of insulin secretion. Since this neuropeptide does not modify glucagon or somatostatin release, a direct effect of galanin on the B-cell seems plausible.     

Effects of gastric inhibitory polypeptide, vasoactive intestinal polypeptide and peptide histidine isoleucine on the secretion of hormones by isolated mouse pancreatic islets

The release of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) by isolated mouse pancreatic islets was determined during 30-min incubations at 5.6 and 16.7 mmol glucose/l in the absence and presence of gastric inhibitory polypeptide (GIP), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) at concentrations of 1-1000 nmol/l. Insulin release was enhanced (greater than 50%) by GIP (100-1000 nmol/l) and VIP (1 mumol/l) at 5.6 mmol glucose/l, but not at 16.7 mmol glucose/l. Glucagon release was increased by GIP (100-1000 nmol/l), and by VIP and PHI (1-1000 nmol/l) at both glucose concentrations in a dose-related manner (maximum increases greater than tenfold). Somatostatin release was similarly increased by GIP (10-1000 nmol/l) at both glucose concentrations. Only the highest concentration (1 mumol/l) of PHI tested increased somatostatin release (twofold) at 5.6 mmol glucose/l, whereas PHI and VIP (1-1000 nmol/l) reduced (greater than 37%) somatostatin release at 16.7 mmol glucose/l. PP release was increased (49-58%) by 100-1000 nmol GIP/l, but was not significantly altered by VIP, and was reduced (39-56%) by PHI. The results indicate that GIP, VIP and PHI each stimulate glucagon release in a dose-related manner, but they exert discretely different effects on other islet hormones depending upon the dose and the prevailing glucose concentration.     

Porcine pancreastatin has no effect on endocrine secretion from the pig pancreas

Summary We investigated the effects of porcine pancreastatin on the endocrine and unstimulated exocrine secretion of isolated, perfused porcine pancreas. Pancreastatin in a concentration of 10^–8mol/l had no effect on basal secretion of insulin, glucagon and somatostatin at a perfusate glucose concentration of 5 mmol/l (n=4) and neither at 10^–8 nor 10^–7 mol/l influenced the hormone responses to acute elevations of perfusate glucose concentration from 3.5 to 11 mmol/l (n=7). This elevation strongly stimulated insulin secretion and inhibited glucagon secretion. Exocrine secretion was not affected by pancreastatin. The results suggest that pancreastatin does not directly influence pancreatic secretion.     

Pancreastatin and islet hormone release.

The effect of pancreastatin on the release of insulin, glucagon, and somatostatin was studied in the isolated perfused rat pancreas. After an initial equilibration period (-20 to 0 min) with a basal glucose concentration (3.3 mM), the pancreata were perfused with either 16.7 mM glucose (0-40 min) or with 20 mM arginine (0-20 min). Pancreastatin was introduced 10 min prior to and throughout the administration of the high glucose and arginine and continued during their perfusion. As expected, the glucose and the arginine augmented insulin and somatostatin release. Pancreastatin (1 and 10 nM) markedly suppressed the first phase of insulin release with both insulinogogues used, while the early somatostatin secretion was not significantly decreased. However, the peak incremental somatostatin response to arginine was reduced by 50% (P less than 0.05). Conversely, the peptide (10 nM) tended to augment arginine-induced glucagon release. Pancreastatin (100 nM) also suppressed glucose-stimulated insulin release from isolated rat islets. These pancreastatin-mediated alterations in islet hormone release are reminiscent of those known to characterize non-insulin-dependent diabetes. Therefore, the significance of pancreastatin in islet physiology and pathophysiology deserves special consideration.     

Effects of rat pancreatic polypeptide on islet-cell secretion in the perfused rat pancreas.

Pancreatic polypeptide (PP) secretory cells are abundant in the islets of Langerhans. Results concerning the effects of exogenous PP on islet-cell secretion are controversial. This might be due in part to species specificity, given that most reports refer to studies performed using PP of bovine, porcine, or human origin in a heterologous animal model. Thus, we have investigated the influence of synthetic rat PP (80 nmol/L) on unstimulated insulin, glucagon, and somatostatin release, and on the responses of these hormones to glucose (11 mmol/L) and to arginine (3.5 mmol/L) in a homologous animal model, the perfused rat pancreas. Infusion of rat PP (rPP) reduced unstimulated insulin release by 35% (P = .03), and the insulin responses to glucose by 65% (P = .029) and to arginine by 50% (P = .026), without modifying glucagon output. rPP did not affect somatostatin secretion, either in unstimulated conditions or in the presence of 11 mmol/L glucose. However, it induced a clear-cut increase in somatostatin release during 3.5 mmol/L arginine infusion. Our observation that rPP inhibited insulin secretion without affecting glucagon and somatostatin output points to a direct effect of PP on B-cell function. However, during aminogenic priming of the D cell, the inhibition of insulin output induced by rPP was accompanied by an increase in somatostatin release. Thus, in this circumstance, it might be considered that the blocking effect of PP on B-cell secretion could be, at least in part, mediated by a D-cell paracrine effect.     

Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide,inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas

Aims/hypothesis  The glucose-lowering effect of glucagon-like peptide-1 (GLP-1) is based not only upon its potent insulinotropic actions but also on its ability to restrain glucagon secretion. Surprisingly, the closely related glucose-dependent insulinotropic peptide (GIP) stimulates glucagon release. We examined whether the islet hormone somatostatin, which strongly inhibits glucagon secretion, is involved in this divergent behaviour. Methods  At 1.5 mmol/l glucose and therefore minimal insulin secretion, the glucagon, insulin and somatostatin responses to 20 mmol/l glucose, GLP-1, GIP and somatostatin were studied in the presence of a high-affinity monoclonal somatostatin antibody and of a highly specific somatostatin receptor subtype 2 (SSTR2) antagonist (PRL-2903) in the isolated perfused rat pancreas. Results  In control experiments, GLP-1 at 1 and 10 nmol/l reduced glucagon secretion significantly to 59.0 ± 6.3% (p < 0.004; n = 5; SSTR2 series; each vs pre-infusion level) and to 48.0 ± 2.6% (p < 0.001; n = 6; somatostatin antibody series) respectively. During somatostatin antibody administration, GLP-1 still inhibited glucagon secretion significantly, but the effect was less pronounced than in control experiments (p < 0.018). Co-infusion of the SSTR2 antagonist completely abolished the GLP-1-induced suppression of glucagon secretion. In contrast, neither the GIP-induced stimulation of glucagon release nor its inhibition by 20 mmol/l glucose was altered by somatostatin antibody or SSTR2 antagonist administration. Conclusions/interpretation  We conclude that GLP-1 is capable of inhibiting glucagon secretion even in the absence of secretory products from the beta cell. It is highly likely that this is mediated via somatostatin interacting with SSTR2 on rat alpha cells. In contrast, GIP and glucose seem to influence the alpha cell independently of somatostatin secretion.     

Effect of pancreastatin on insulin secretion and the exocrine pancreas in rats]

Pancreastatin, a 49-amino-acid C-terminal amidated peptide, was isolated from porcine pancreas in 1986. It has been reported to inhibit insulin release and exocrine pancreatic secretion, but both these effects have been disputed. In the isolated perfused rat pancreas we therefore studied the effect of pancreastatin on insulin and exocrine pancreatic secretion. Neither basal exocrine pancreatic secretion, nor exocrine secretion stimulated by CCK-8, bombesin or secretin were affected by pancreastatin. 20 or 200 pM pancreastatin, however, significantly inhibited stimulated insulin release. We conclude that pancreastatin seems to be yet another inhibitory peptide, which--for unknown reasons--inhibits insulin release both in vivo and in vitro, but exocrine pancreatic secretion only 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.     

Pancreastatin-like immunoreactivity and insulin are released in parallel from the perfused porcine pancreas

Pancreastatin, a peptide isolated from the porcine pancreas, suppresses insulin release from pancreatic islets of the rat. Pancreastatin immunoreactivity has been localized to islet B and D cells in the porcine pancreas. We have developed a RIA for this peptide, using rabbit anti-porcine pancreastatin antibodies and 125I-Tyr-pancreastatin. Isolated pig pancreata were perfused with a nonrecirculating bicarbonate buffer solution containing 4% Dextran and 0.1% Albumin. Glucose (11 mmol/liter) induced a biphasic release of pancreastatin-like immunoreactivity (PLI). Electrical stimulation of the vagus nerves (8 Hz), as well as perfusion with acetyl choline (10(-6) mol/liter) in the presence of 5.5 mmol/liter glucose, also evoked prompt PLI responses. Furthermore, truncated GLP-1 (proglucagon 78-107; 10(-9) mol/liter) induced PLI release. All tested stimuli also elicited insulin secretion. To investigate whether the PLI measured could be ascribed to secretion of the low molecular weight pancreastatin (Mr 5,100) or to a possible precursor such as chromogranin A (Mr approximately 75,000), perfusates containing PLI were subjected to gel filtration on an Ultropac G3000SW column. All of the PLI was recovered at the elution position of the pancreastatin marker. In conclusion, PLI and insulin are released in parallel from the perfused porcine pancreas, exposed to stimuli known to affect insulin release.     

Effects of porcine pancreastatin on secretion and biosynthesis of insulin and glucose oxidation of isolated rat pancreatic islets

The effects of porcine pancreastatin were studied on insulin secretion induced by glucose and nonnutrient stimuli, insulin biosynthesis, and glucose oxidation of cultured rat islets. Pancreastatin (100 nM) significantly suppressed, by 32-52%, the insulin response to 27, 16.7, 11, and 5.5 mM but not to 50 mM glucose, whereas 10 nM pancreastatin inhibited insulin release significantly only at 11 and 5.5 mM glucose. Pancreastatin (10 and 100 nM) also suppressed release induced by 20 mM arginine (by 26 and 30%) as well as by 1 microgram/ml of glibenclamide (by 56 and 72%, respectively). Pancreastatin (10 and 100 nM) furthermore inhibited insulin release induced by 0.1 mM 3-isobutyl-1-methylxanthine (IBMX) (by 40 and 61%, respectively) and 1.0 mM IBMX (by 44 and 76%, respectively). Neither glucose oxidation nor overall insulin biosynthesis in islets was significantly affected by pancreastatin, although a slight but significant enhancement of biosynthesis was noted at 1.7 mM glucose in the presence of 100 nM pancreastatin. In conclusion, these data demonstrate that porcine pancreastatin suppresses glucose-induced insulin response from isolated rat islets in a competitive manner. This effect seems not to be exerted through a suppression of (pro)insulin biosynthesis or glucose metabolism in the islets, and thus the effect mediated by pancreastatin must be on a step distal to the coupling between islet glucose metabolism and insulin secretion. The relatively strong inhibition by the peptide of IBMX-induced insulin release suggests that it acts on the cAMP system of islet B cells.     

Effect of GIP on the secretion of insulin and somatostatin and the accumulation of cyclic AMP in vitro in the rat

The effects of gastric inhibitory polypeptide (GIP) on insulin secretion as well as on the intra-islet accumulation of [3H]cyclic AMP were investigated in isolated pancreatic islets of the rat. In the presence of 6.7 mmol/l of glucose, 3.0 and 30 nmol/l of GIP induced both insulin and [3H]cyclic AMP responses, while lower and higher concentrations of the peptide were ineffective. A coupling of the two parameters was also found with regard to interaction between glucose and GIP. Thus while 30 nmol/l of GIP was stimulatory together with 6.7, 16.7 or 33.3 mmol/l of glucose, the peptide stimulated neither insulin release, nor the accumulation of [3H]cyclic AMP in the presence of a low concentration of glucose (3.3 mmol/l). The concomittant release of insulin and somatostatin was studied in the perfused pancreas in order to assess a possible influence by somatostatin on the dose-response pattern for GIP-induced insulin release. In this preparation 1.0 to 10 nmol/l of GIP stimulated insulin and somatostatin secretion; however while these concentrations were equipotent on insulin release, 10 nmol/l of GIP stimulated somatostatin release more than 1 nmol/l, indicating differences in dose-response curves for the GIP-induced stimulation of the two hormones. It is concluded that 1) modulation of GIP-induced insulin release is coupled to changes in cyclc AMP response in the islet, 2) GIP-induced somatostatin secretion may influence the concomittant insulin response.     

Interaction of glucagon-like peptide-1(7-36) amide and gastric inhibitory polypeptide or cholecystokinin on insulin and glucagon secretion from the isolated perfused rat pancreas.

The interaction of three incretin candidates, glucagon-like peptide-1(7-36)amide (t-GLP-1), gastric inhibitory polypeptide (GIP), and sulfated COOH-terminal octapeptide of cholecystokinin (CCK-8-S), on insulin and glucagon release from the isolated perfused rat pancreas was studied. Under the perfusate condition of 8.3 mmol/L glucose, coinfusion of 0.1 nmol/L t-GLP-1 and 0.1 nmol/L GIP resulted in an augmented insulin release greater than that obtained by the same dose of each peptide alone. The degree of stimulation elicited by t-GLP-1 and GIP reached a plateau at 0.3 nmol/L for both infusates, and no cooperative effect was observed by coinfusion at 0.3 nmol/L. Coinfusion of 0.1 nmol/L t-GLP-1 and and 0.1 nmol/L CCK-8-S also resulted in an augmented insulin release greater than that obtained by the same dose of each peptide alone. A similar cooperative effect was observed by coinfusion at 0.3 nmol/L, 1 nmol/L, and 3 nmol/L. With the same perfusion experiments, glucagon release was not significantly affected by any peptide at concentrations of 0.1, 0.3, 1, or 3 nmol/L. The coinfusion of 1 nmol/L t-GLP-1 and GIP elicited a transient, but significant, increase in glucagon release. A similar result was obtained by the coinfusion of 0.3 nmol/L and 3 nmol/L t-GLP-1 and GIP, respectively. The coinfusion of t-GLP-1 and CCK-8-S did not affect the glucagon release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stimulatory effect of pancreastatin on gastric acid secretion in conscious dogs

Pancreastatin, a new 49-amino acid peptide, has recently been isolated and characterized from extracts of the porcine pancreas. The objective of the present study was to examine the effect of various doses of pancreastatin on gastric acid secretion in conscious dogs that were prepared with chronic gastric cannulas. Pancreastatin, administered IV at 400 pmol.kg-1 x h-1, enhanced peptone meal [peptone (5%), phenylalanine (90 mmol/L), glucose (12 g/dL)]-stimulated gastric acid secretion by 50%; pancreastatin at 800 pmol.kg-1 x h-1 enhanced peptone meal secretion by 165% (P less than 0.05). Intravenous administration of pancreastatin did not affect basal or peptone-stimulated release of gastrin. In addition, IV pancreastatin (400 pmol.kg-1 x h-1) failed to influence basal gastric acid secretion. Pancreastatin did not affect acid secretion stimulated by 2-deoxyglucose, histamine, or pentagastrin. The present study shows that pancreastatin can selectively enhance gastric acid secretion by a mechanism independent of cholinergic, histaminergic, or gastrin input.     

Influence of glucagon, gastric inhibitory polypeptide, pancreatic polypeptide and somatostatin on beta-adrenergically induced insulin secretion in the mouse

The effect of four polypeptides, glucagon, Gastric Inhibitory Polypeptide (GIP), Pancreatic Polypeptide (PP) and somatostatin on beta-adrenoceptor stimulated insulin secretion in vivo in the mouse was investigated. The beta-adrenoceptor stimulation was induced by isoprenaline (IPNA). It was found that at dose levels without influence on basal insulin secretion the polypeptides produced the following pattern of interaction with IPNA. Insulin secretion induced by IPNA was increased by glucagon and inhibited by somatostatin. GIP and PP did not change IPNA-induced insulin release. It is concluded from this and earlier published studies that glucagon, but not always GIP, serves as a positive modulator of basal and stimulated insulin secretion, and that somatostatin is a general inhibitor of insulin release. beta-Adrenoceptor-induced insulin secretion however, seems to be less sensitive to somatostatin than insulin release induced by glucose.     

Cholecystokinin-33 potentiates and vasoactive intestinal polypeptide inhibits gastric inhibitory polypeptide--induced insulin secretion in the perfused rat pancreas

Gastric inhibitory polypeptide (GIP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) stimulate insulin secretion. In this study we investigated whether CCK-33 and VIP could influence the insulinogenic effect of simultaneously administered GIP and 6.7 mmol/l glucose in the perfused rat pancreas. We found that at 0.1 nmol/l, GIP markedly potentiated glucose-induced insulin release whereas CCK-33 and VIP had a weak stimulatory effect and only during the late phase. At this low dose level, CCK-33 potentiated but VIP inhibited the late phase of insulin release stimulated by glucose and GIP. At 1.0 nmol/l, GIP, CCK-33, and VIP markedly potentiated both phases of glucose-induced insulin secretion. At this dose level CCK-33 and GIP exerted additive stimulatory effects on the late phase of insulin release triggered by glucose. In contrast, 1.0 nmol/l VIP inhibited insulin secretion augmented by glucose and GIP. In summary 1) GIP, CCK-33 and VIP all potentiate glucose-induced insulin secretion from the perfused rat pancreas, and 2) CCK-33 potentiates and VIP inhibits GIP-induced insulin secretion. We suggest that interactions of this kind are of importance for the precise regulation of insulin secretion.     

Pancreastatin, a presumed product of chromogranin-A (secretory protein-I) processing, inhibits secretion from porcine parathyroid cells in culture

Chromogranin-A, also referred to as secretory protein-I, is a 50K protein found in and secreted by endocrine cells, in which it is costored with the native hormone. Porcine chromogranin-A contains a sequence identical to pancreastatin, a 49-amino acid, C-terminally amidated peptide that has been isolated from porcine pancreas, suggesting that chromogranin-A is the precursor of pancreastatin. Pancreastatin has been found to be a potent inhibitor of glucose-stimulated insulin release. As it is possible that pancreastatin inhibits secretion from other chromogranin-A-containing tissues in which it may be formed, we tested its action on dispersed porcine parathyroid cells in culture. Secretion of chromogranin-A and PTH was up to 6-fold greater at 0.5 mM Ca2+ than at 3.0 mM Ca2+. Pancreastatin (1 nM) reduced the secretion of both chromogranin-A and PTH at 0.5 mM Ca2+ to approximately the levels found at 3.0 mM Ca2+, but did not affect secretion at 3.0 mM Ca2+. Pancreastatin (0.01-1.0 nM) inhibited secretion of chromogranin-A in a dose-dependent fashion. Preincubation of the cells with pancreastatin was not required for inhibition. Transfer of inhibited cells to medium without pancreastatin led to restoration of secretion within 90 min. Phorbol myristate acetate (1.6 microM) stimulated secretion of PTH and chromogranin-A at 3.0 mM Ca2+, but not at 0.5 mM Ca2+. Pancreastatin reversed this stimulation, demonstrating that its inhibition was independent of Ca2+ concentration. These results are consonant with pancreastatin playing a physiological role in modulation of secretion by the parathyroid and, by extension, other endocrine tissues.     

Fat-induced jejunal inhibition of gastric acid secretion and release of pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide, and vasoactive intestinal polypeptide in man.

The effect of intrajejunal (i.j.) infusion of fat on meal-stimulated gastric acid secretion and release of pancreatic glucagon (PG), enteroglucagon (EG), gastric inhibitory polypeptide (GIP), and vasoactive intestinal polypeptide (VIP) was studied in seven healthy volunteers. I.j. fat markedly inhibited meal-stimulated acid secretion as compared to a control study with i.j. saline infusion. The acid inhibition was accompanied by augmental plasma concentrations of EG, GIP, and VIP but not of PG, suggesting that EG, GIP, and VIP may be among mediators of fat-induced jejunal inhibition of acid secretion. Concentration-time relationship makes it unlikely that the observed inhibition could be ascribed to any single peptide studied.     

Correlation of endogenous somatostatin, gastric inhibitory polypeptide, glucagon and insulin with gastric function in the conscious calf

Levels of endogenous somatostatin, gastric inhibitory polypeptide (GIP), glucagon and insulin were measured during gastric (abomasal) emptying in the conscious calf. Isotonic NaHCO3 infused into the duodenum increased rates of emptying of a saline test meal and of gastric acid secretion, but had no effect on basal levels of blood glucose, somatostatin, GIP, insulin or glucagon. By contrast, intraduodenal infusion of 60 mM-HCl caused complete inhibition of gastric emptying, reduction of acid secretion, and an immediate increase in plasma somatostatin from 121.3 +/- 9.4 (S.E.M.) to 286.3 +/- 16.3 pg/ml (P less 0.01) but levels of GIP, insulin, glucagon and glucose were unaltered. Intravenous injection of somatostatin (0.5 microgram/kg) suppressed the antral electromyographic recording and gastri efflux so long as plasma somatostatin levels remained above approx. 200pg/ml. This suggest that somatostatin can be released by intraduodenal acidification and that it inhibits gastric function by an endocrine effect. Since somatostatin retards gastric emptying it may therefore have an indirect role in nutrient homeostasis by limiting discharge of gastric chyme to the duodenum.     

The interaction of Vasoactive Intestinal Polypeptide (VIP), glucose and arginine on the secretion of insulin,glucagon and somatostatin in the perfused rat pancreas

Summary Vasoactive Intestinal Polypeptide (VIP) increased the release of insulin, glucagon and somatostatin from the perfused rat pancreas. The amount of these hormones released was dependent upon the prevailing glucose concentration. VIP stimulated glucagon release in the absence of glucose, while insulin and somatostatin release were increased by VIP only in the presence of glucose concentrations of 4.4 mmol/l and above. Glucagon secretion stimulated by arginine in the presence of 4.4 mmol/l glucose was potentiated by VIP. In contrast, VIP did not induce any further increase in the secretion of insulin and somatostatin over that stimulated by arginine. At higher concentrations of glucose (6.7, 16.7, and 33.3 mmol/l) VIP continued to stimulate insulin and somatostatin release, this effect being synergistic on early-phase insulin release. The effects of VIP on islet cells thus depend on the levels of modulating nutrients.     

Vagal control of the release of somatostatin, vasoactive intestinal polypeptide, gastrin-releasing peptide, and HCl from porcine non-antral stomach.

We studied the secretion of somatostatin and HCl and the release of vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP) from isolated, vascularly perfused, porcine non-antral stomach. Electric vagus stimulation increased acid secretion and the release of VIP and GRP and inhibited somatostatin secretion as determined in the venous effluent. Atropine abolished the HCl response and reversed the somatostatin inhibition to a three-fold increase, whereas GRP and VIP responses were unchanged. Both intra-arterial carbachol (10(-6) M) and GRP (10(-8) M) increased acid secretion and inhibited somatostatin secretion. VIP (10(-8) M) increased somatostatin secretion and had no effect on acid secretion. By immunohistochemistry, somatostatin was localized to both open-type and closed-type cells equally spread in the various parts of the gastric glands without particular relation to the parietal cells. Numerous GRP- and VIP-immunoreactive nerve fibers were seen between the glands. It is concluded that the fundic and antral secretion of somatostatin, investigated in a previous study, are differently regulated. The relation of fundic somatostatin release to acid secretion seems to be complex.