Forskolin induced chloride secretion across the isolated mucosa of rat colon descendens

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Abstract
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 differences (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 (5x10−6 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.