Effects of ethanol on meal-stimulated secretion of pancreatic polypeptide and cholecystokinin: comparison of healthy volunteers, heavy drinkers, and patients with chronic pancreatitis.
Tiscornia and Dreiling (Physiopathogenic Hypothesis of Alcoholic Pancreatitis: Supranormal Ecbolic Stimulation of the "Pancreon" Units Secondary to the Loss of the Negative Component of Pancreas Innervation. Pancreas 1987;2:604-612.) proposed that hypertonicity of intrapancreatic cholinergic neurons provoked by chronic alcoholism may contribute to the pathogenesis of chronic pancreatitis (CP). In the present study, the validity of this hypothesis was investigated in humans by studying the effects of atropine, cisapride, and ethanol on the meal-stimulated secretion of pancreatic polypeptide (PP) and cholecystokinin (CCK) in healthy volunteers, heavy drinkers, and CP patients. In healthy volunteers, the early phase PP response (0-40 min) to a test meal was completely blocked by atropine, whereas it was augmented by cisapride, an enhancer of acetylcholine release from cholinergic nerves. The early phase PP response to a test meal was inhibited by ethanol in healthy volunteers, whereas, in heavy drinkers, the response was augmented and the inhibition by ethanol was abrogated. In CP patients, ethanol tended to enhance the early phase PP response. Ethanol did not affect the early phase CCK response to a test meal in any group, but it significantly enhanced the late phase CCK response (40-120 min) in CP patients. These results suggest that: (i) oral ethanol may inhibit the postprandial activation of the cholinergic neural pathway to the pancreas in healthy subjects, (ii) in heavy drinkers, postprandial cholinergic tone may be augmented and become resistant to the inhibition by ethanol, and (iii) the ethanol-induced increase in the postprandial CCK response in CP patients may play some role in the pathophysiology of this disease.
Hirano
H
H
Third Department of Internal Medicine, Tohoku University School of Medicine, Miyagi, Japan.
Shimosegawa
T
T
Meguro
T
T
Shiga
N
N
Koizumi
M
M
Toyota
T
T
D000328:Adult; D000437:Alcoholism / Q000378:metabolism* / Q000503:physiopathology; D000704:Analysis of Variance; D001285:Atropine / Q000494:pharmacology; D002766:Cholecystokinin / Q000097:blood* / Q000187:drug effects; D002908:Chronic Disease; D020117:Cisapride; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010191:Pancreatic Polypeptide / Q000097:blood* / Q000187:drug effects; D010195:Pancreatitis / Q000378:metabolism / Q000503:physiopathology*; D010277:Parasympathomimetics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology; D011863:Radioimmunoassay
D010277:Parasympathomimetics; D010880:Piperidines; D000431:Ethanol; D010191:Pancreatic Polypeptide; D001285:Atropine; D002766:Cholecystokinin; D020117:Cisapride