Cholinergic stimulation and inhibition of pancreatic secretion in alcohol-adapted dogs.
There is indirect evidence of increased release of acetylcholine in the exocrine pancreas of chronically alcoholic dogs. Our aim was to ascertain whether altered pancreatic responsiveness to cholinergic stimulation was an associated phenomenon. Pancreatic dose-response tests with graded bethanechol stimulation on constant secretion stimulation, without or with a low dose of background atropine, were performed in four chronic gastric and duodenal fistula dogs after 3 and 12 months of intragastric feeding with ethanol. The secretory protein response was dose-dependently increased by bethanechol in the control dogs but not in the test dogs, after 3 or 12 months of daily alcohol. They responded significantly only to a dose four to eight times greater than the minimum effective dose in the control dogs. Atropine depressed the entire dose-response curve of these dogs but only the response to the greatest doses in the alcohol-treated dogs. In previous experiments caerulein and/or secretin evoked increased secretory responses of bicarbonate in chronically alcoholic dogs, but this was not the case in this study with bethanechol, which did not have a stimulating effect on bicarbonate in either test or control dogs. Concomitant atropine, however, unmasked a bicarbonate-stimulating effect of bethanechol in control but not in treated dogs. It is concluded that chronic alcohol-feeding, already after 3 months, leads to a diminished pancreatic responsiveness to cholinergic stimulation and inhibition of protein output, as evidenced by at least a fourfold increase of the minimum effective dose of bethanechol and diminished inhibitory action of atropine.
D000222:Adaptation, Physiological / Q000187:drug effects; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001626:Bethanechol Compounds / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D004285:Dogs; D006801:Humans; D010179:Pancreas / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects*; D012633:Secretin / Q000494:pharmacology; D013997:Time Factors
D001626:Bethanechol Compounds; D001639:Bicarbonates; D011506:Proteins; D011950:Receptors, Cholinergic; D012633:Secretin; D001285:Atropine