Gastrin in clinical gastroenterology: Recent developments

274 GASTRIN IN CLINICAL GASTROENTEROLOGY : RECENT DEVELOPMENTS Walsh JH, CURE/UCLA digestive Disease Center, West Los Angeles VA Center, Los Angeles, CA, 90073, USA During the past few years, identification of Helicobacter pylori infection as the factor responsible for abnormal gastrin secretion in peptic ulcer disease, the trophic effect of gastrin on ECL cells and association of ECL cell hyperplasia and gastric carcinoid tumors with chronic hypergastrinemia, minimal changes in ECL density in patients after chronic treatment with potent antisecretory agents, improved surgical success in resection of gastrinomas, secretion of incompletely processed gastrin by gastrinomas and in other conditions of pathological hypergastrinemia, incompletely processed progastrin in various nongastric tissues and non-GI malignancies, and controversy surrounding the role of gastrin as a growth factor in colon cancer have been areas in which significant new clinically relevant information has been obtained. Some has been obtained because of advances in molecular and immunological techniques for detection of gastrin gene products. The discovery of carcinoid tumors in rats treated lifelong with potent antisecretory agents has led to renewed interest in the pathological and physiological role of gastrin as atrophic agent. Recent observations that humans infected with Helicobacter pylori have hypergastrinemia that can be reversed by bacterial eradication will necessitate revised concepts of regulation of gastrin release in peptic ulcer disease. Gastrin continues to be the hormone most relevant to clinical gastrointestinal disorders.

INTERACTION OF CHOLECYSTOKININ (CCK) AND ACETYLCHOLINE (ACh) ON INTRACELLULAR FREE CALCIUM IN INDIVIDUAL RAT PANCREATIC/3-CELLS Wang J, Brown JC, MRC Regulatory Peptide Group, University of Britisch Columbia, Vancouver, B.C. Canada V6T 1Z3 The interaction between CCK and ACh on cytosolic free calcium ion concentration ([Ca2+]i) in individual fura-2-1oaded rat pancreatic /3-cells has been studied. Approximately 90 % of the /3cells responded to both CCK and ACh in a dose-dependent manner in the presence of 4.4 mM glucose. In the cells which responded to both CCK and ACh, proglumide (10-aM), a CCK receptor antagonist, abolished the CCK-induced increase in [Ca2+]i without affecting the action of ACh, while atropine (10-7M) blocked only the ACh-induced [Ca2+]i increase. Perifusion of the cells with 10-5M ACh or 10-SM CCK caused a transient increase in [Ca2+]i. The increase in [Ca2+]i returned to resting levels despite the continued presence of ACh or CCK. A bolus application of 100 #1 10-3M ACh failed to increase [Ca2+]i during the perifusion with 10-SM ACh. In contrast, a bolus application of 100 #l of CCK (10-6M) resulted in a transient increase in [Ca2+]i when superimposed on a perifusion with 10-8M CCK. Perifusion with one agonist not only modulated its own action, but also influenced the response to the other agonist, e.g., the ACh-induced [Ca2+]i response was significantly decreased (>25 %) during the perifusion with CCK. These data indicate that the stimulation of [Ca2+]i increase by CCK and ACh in/~-cells was mediated by their receptors and regulated by auto-feedback mechanisms.