Forskolin induced chloride secretion across the isolated mucosa of rat colon descendens.
The effects of forskolin, a diterpene reported to stimulate adenylate cyclase, on electrolyte transport across the isolated colonic mucosa of rat colon descendens were investigated. Forskolin, over a concentration range of 10(-7)-10(-5) M, dose-dependently increased short circuit current (Isc) and transmural potential difference (Vms). The nearly 2-fold increase in Isc and Vms caused by forskolin was accompanied by a small increase in transmural conductance (Gt). The effects of forskolin were rapid and completely reversible without any loss in tissue sensitivity. Forskolin (5 X 10(-6) M) inhibited the absorption of Na+ and reversed Cl- absorption to secretion. These effects were due to an inhibition of the mucosal-to-serosal fluxes of Na+ and Cl-. Ion substitution experiments revealed that the effects of forskolin were both Na+ and Cl- dependent and these ions were required in the serosal solution. Furosemide (10(-4) M) as well as scilliroside (10(-4) M) reversed and prevented the increase in Isc caused by forskolin. Adenylate cyclase activity in homogenates of colonic mucosa was increased 3-fold by forskolin. These results with rat colon are compared with those reported for rabbit colon and ileum and the mechanism of cyclic-AMP induced Cl- secretion in these epithelia is discussed.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002018:Bufanolides / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin; D003106:Colon / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains
D002018:Bufanolides; D002712:Chlorides; D004224:Diterpenes; D005576:Colforsin; C022879:scilliroside; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases