Inhibition by propranolol of bile acid stimulation of rabbit colonic adenylate cyclase in vitro.
Bile acids, especially unconjugated deoxycholic acid, cause diarrhea by inducing colonic mucosal secretion of water and electrolytes. This effect has been shown to be mediated by adenylate cyclase (AC). Propranolol, a beta-adrenergic blocking agent which inhibits AC, may then prevent this action of bile acids on colonic mucosa. The aim of this study was to determine the effect of bile acids, catecholamines, and propranolol on AC activity in colonic mucosa. The in vitro effects of deoxycholic acid, taurocholic acid, NaF, epinephrine, norepinephrine, and propranolol on AC in rabbit colonic mucosa were determined. NaF, 10(-4) M, increased AC activity to 220% of control (P less than 0.01). Deoxycholic acid, 10(-4) M, increased AC activity to 178% of control (P less than 0.01). Lesser but significant (P less than 0.01) stimulation of AC occurred at both higher and lower concentrations of deoxycholic acid, with no effect at 10(-10) M. Taurocholic acid, 10(-4) M, and epinephrine and norepinephrine, 10(-2) M, 10(-4) M, 10(-6) M, and 10(-8) M, had no effect on AC. Propranolol, 10(-6) M, caused a 60% decrease (P less than 0.01) in the stimulated AC activity induced by 10(-4) M deoxycholic acid. Propranolol, 10(-4) M, decreased basal AC by 30% (P less than 0.01).


CONCLUSIONS
(1) Deoxycholic acid, but not taurocholic acid, epinephrine, or norepinephrine, stimulates colonic AC activity. (2) Propranolol inhibited this deoxycholic acid stimulation of AC. (3) Catecholamines are not intermediaries in this action of propranolol on colonic mucosal AC activity.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D003106:Colon / Q000201:enzymology*; D000242:Cyclic AMP / Q000096:biosynthesis; D003840:Deoxycholic Acid / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D011817:Rabbits; D013656:Taurocholic Acid / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D001647:Bile Acids and Salts; D003840:Deoxycholic Acid; D013656:Taurocholic Acid; D011433:Propranolol; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D009638:Norepinephrine; D004837:Epinephrine