Control of exocrine secretion in the guinea-pig pancreas by histamine H₃receptors

Abstract

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.

Regulation of Pancreatic Secretion

“…Mast cells are primarily located around blood vessels in the pancreas and are less abundant in the acinar and endocrine portions of the gland. 234 The effects of histamine were dose dependent, however. Pancreatic acinar cells express both H1 and H2 histamine receptors.…”

“…Histamine immunoreactive mast cells are distributed throughout the pancreas in many species including humans, dogs, fox, sheep, pigs, cattle, and rats. 234 Histamine is found in pancreatic juice of dogs following stimulation with secretin or pilocarpine. Mast cells are primarily located around blood vessels in the pancreas and are less abundant in the acinar and endocrine portions of the gland.…”

The physiological role of histamine in the exocrine pancreas

“…Similarly, in the anaesthetized guinea pig, thioperamide can block the inhibitory effect of (R)-alpha-methylhistamine on pancreatic juice flow and total protein output. These results suggest that stimulation of H 3 receptors in the pancreas may result in a decrease in fluid, enzyme and protein secretion by inhibition of acetylcholine release from intrinsic pancreatic nerves [80][81][82]. Taken together, these findings indicate that like in other tissues [11-14, 77, 78], histamine may be an important physiological mediator between nerves and the effector tissue in the exocrine pancreas.…”

“…Histamine H 3 receptor agonist (R)-alpha-methylhistamine can elicit a dose dependent increase in amylase secretion and total protein output in isolated guinea pig segments [82]. The H 3 receptor antagonist, thioperamide blocked the secretory effects of (R)-alpha-methylhistamine.…”

“…There is also emerging evidence that H 3 receptors may exist in the gastrointestinal tract on nonneuronal cells and they may directly be involved in controlling gastric acid secretion [77][78][79]. The potential physiological and pharmacological roles of histamine acting at the H 3 receptor using specific H 3 receptor drugs in the regulation of exocrine pancreatic secretion in the guinea pig were investigated in a previous study [23,[80][81][82].…”