Colonic cyclic AMP metabolism following chronic ethanol consumption in the rat: effect of hormonal secretagogues.
The colonic cyclic AMP system is known to be involved in intestinal secretion and can be stimulated by a variety of gastrointestinal hormones including prostaglandins. We have investigated the effect of chronic ethanol ingestion on the activity of the key enzymes in cyclic AMP metabolism--adenylate cyclase and cyclic AMP phosphodiesterase--in the colonic mucosa of the rat. Chronic ethanol consumption by feeding a nutritionally adequate liquid diet enhanced basal colonic adenylate cyclase activity significantly by 168% (p less than 0.01), but had no effect on colonic low Km cyclic AMP phosphodiesterase activity. In addition, various hormonal secretagogues were used to stimulate colonic adenylate cyclase. Colonic adenylate cyclase exhibited a significantly greater sensitivity and efficacy to prostaglandins and vasoactive intestinal peptide after chronic ethanol ingestion. Since increased intestinal cyclic AMP production due to an increased activity of intestinal adenylate cyclase is known to promote intestinal secretion of water and electrolytes, the frequently observed diarrhea in alcoholics may be explained at least in part by an enhanced production of colonic cyclic AMP.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000437:Alcoholism / Q000201:enzymology*; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000201:enzymology*; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D011464:Epoprostenol / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D005768:Gastrointestinal Hormones; D011458:Prostaglandins E; D014660:Vasoactive Intestinal Peptide; D011464:Epoprostenol; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D015232:Dinoprostone