SUMMARYThis study investigates the interaction between physiological doses of the synthetic gut hormones, cholecystokinin-octapeptide (CCK8) and secretin on pancreatic juice secretion in the anaesthetized rat and on amylase secretion and Ca2l and Mg2+ mobilization in isolated pancreatic segments and acinar cells. CCK8 (150 pmol kg-1 h-1) and secretin (100 pmol kg-1 h-1) evoked marked time course increases in pancreatic juice flow, total protein output and amylase secretion in the anaesthetized rat when administered separately compared to saline controls. Simultaneous intravenous infusion of CCK8 and secretin did not yield either an additive response or a potentiation but instead it caused a decrease in secretory responses. Administration of either polymyxin B (10-8 mol kg-1 h-1) or staurosporine (10-8 mol kg-1 h-1), two protein kinase C inhibitors, simultaneously with both CCK8 and secretin caused a further decrease in all secretory parameters. Superfusing pancreatic segments with either CCK8 (10-1 M) or secretin (10-1 M) elevated amylase output compared to the smaller response with a combination of CCK8 and secretin. Combining staurosporine (10-6 M) with CCK8 and secretin resulted in a further decrease in amylase output. CCK8 (10-1' M) evoked a large increase in radiolabelled Ca2+ influx into pancreatic segments and elevated cytosolic free Ca2+ concentration ([Ca2+]i) in acinar cells loaded with the fluorescent dye, Fura-2. Secretin (10-11 M) alone had no significant effect on Ca2+ mobilization but it markedly attenuated the increases in radiolabelled Ca2+ influx and [Ca2+]i elicited by CCK . In superfused pancreatic segments CCK8 (10-11 M) evoked a net efflux of Mg2+ whereas secretin (10-1' M) induced a net uptake of Mg2+. Combining secretin with CCK8 also resulted in a net uptake of Mg2+. The results indicate that both Ca2+ and Mg2+ mobilization may be associated with the interaction between CCK8 and secretin in the rat pancreas.

SUMMARYAn investigation was made of the effect of histamine on amylase secretion and calcium mobilization in isolated guinea-pig pancreatic segments. The effect of acetylcholine (ACh)

The aim of this study was to investigate the possible involvement of the histamine H 3 receptor in control of exocrine pancreatic secretion from the guinea-pig. In in vitro experiments, the H 3 receptor agonist (R)-α-methylhistamine (0.01-10 µM) elicited a concentration-dependent decrease in the release of α-amylase. (R)-α-Methylhistamine concentrations above 10 µM evoked a concentration-dependent increase in α-amylase secretion. Application of mepyramine (1 µM) partially blocked this increase. The H 3 receptor antagonist thioperamide (1 µM) blocked the effects of (R)-α-methylhistamine below 10 µM. Histamine and (R)-α-methylhistamine attenuated both protein release elicited during electrical-field stimulation and the release of tritiated choline, and these effects were reversed by thioperamide. In an in vivo study, (R)-α-methylhistamine increased juice secretion and total protein content of the juice by 40%. Histamine H 1 and H 2 receptor antagonists blocked this increase and uncovered an attenuation of the secretory parameters (juice flow 28%, total protein content 44%). This attenuation was blocked by thioperamide. These observations suggest that stimulation of the histamine H 3 receptor in the pancreas results in a decreased fluid and enzyme release by inhibition of acetylcholine release from intrinsic pancreatic nerves.Résumé : La présente étude a eu pour objectif d'examiner le rôle possible du récepteur H 3 à l'histamine dans la régulation de la sécrétion pancréatique exocrine du cobaye. Dans des expérience in vitro, l'agoniste du récepteur H 3 , (R)-α-méthylhistamine (0,01-10 µM), a provoqué une diminution concentration-dépendante de la libération d'α-amylase. Des concentrations de (R)-α-méthylhistamine de plus de 10 µM ont induit une augmentation concentration-dépendante de la sécrétion d'α-amylase. L'emploi de mépyramine (1 µM) a partiellement bloqué cette augmentation. L'antagoniste du récepteur H 3 , thiopéramide (1 µM), a bloqué les effets de la (R)-α-méthylhistamine aux doses inférieures à 10 µM. L'histamine et la (R)-α-méthylhistamine ont atténué tant la libération de protéines induite par une stimulation de champ électrique que la libération de choline tritiée, effets qui ont été renversés par le thiopéramide. Dans une étude in vivo, la (R)-α-méthylhistamine a augmenté la sécrétion de suc et la teneur en protéine totale du suc d'environ 40%. Les antagonistes des récepteurs H 1 et H 2 à l'histamine ont bloqué cette augmentation et atténué les paramètres de sécrétion (débit du suc, 28% et teneur protéique totale, 44%). Cette atténuation a été bloquée par le thiopéramide. Ces observations suggèrent que la stimulation du récepteur H 3 à l'histamine dans le pancréas provoque une diminution de la libération d'enzymes et de suc, en diminuant la libération d'acétylcholine des nerfs pancréatiques intrinsèques.

SUMMARYAn investigation was made of the effects of HI and H2 receptor agonists and antagonists on rabbit pancreatic exocrine secretion stimulated by secretin and cholecystokinin (CCK). The HI agonist 2-thiazolylethylamine elicited dose-dependent increases in the rate of secretion. Increases in pancreatic juice flow and enzyme output were also noted after H2 antagonist cimetidine. In contrast, the HI antagonist chlorpheniramine and H2 agonist dimaprit caused reductions in flow and enzyme output. The results suggest that HI receptors have stimulative effects and H2 receptors have inhibitory effects on exocrine rabbit pancreas.

The effects of secretin and cholecystokinin on exocrine pancreas secretion in the guinea pig were investigated. The putative potentiating effect of these two hormones was studied in various settings to elucidate the effect of cholinergic stimuli in such interaction. In anesthetized guinea pig, intravenous infusion of cholecystokinin (0.75 pmol.kg-1.min-1) or secretin (0.5 pmol.kg-1.min-1) resulted in a marked and rapid increase of pancreatic juice flow and protein output. When cholecystokinin was combined with secretin, there was a significant increase in pancreatic, compared with cholecystokinin alone. This increase in pancreatic juice secretion and protein output was significantly suppressed by the prior administration of 100 micrograms/kg atropine. Similar results were obtained when trypsinogen release from pancreatic segments was measured in response to cholecystokinin (32 nM-32 pM) and (or) secretin (1 microM-32 nM). When we assayed the hormonal interaction on amylase release from dispersed pancreatic acini, we found that secretin (32 nM) failed to influence the secretory response to cholecystokinin (1 pM-10 nM). Thus we conclude that a combination of cholecystokinin and secretin resulted in a marked potentiation of the secretory responses in the exocrine guinea pig pancreas by a mechanism that involves cholinergic interactions present at the tissue level but not at the dispersed secretory cell level.