Direct effect of glibenclamide on guanylate cyclase activity in the rat in vitro.

Glibenclamide enhanced the activity in the rat of guanylate cyclase in a number of extra-pancreatic tissues. Thus, glibenclamide enhanced guanylate cyclase activity in vitro two- to threefold in liver, kidney, heart, spleen and colon at a concentration of 1 mumol/l. Dose-response curves of glibenclamide on hepatic guanylate cyclase revealed that more than half-maximal stimulation was observed at a concentration as low as 10 nmol/l (p less than 0.001) and no stimulation of guanylate cyclase was seen when the concentration was decreased to 1 nmol/l. Maximal enhancement was seen at 100 nmol/l of glibenclamide. Varying the concentration of the guanylate cyclase co-factor manganese had no effect on the glibenclamide enhancement of guanylate cyclase. In addition to the increased insulin receptors found recently in monocytes and fibroblasts, the present findings may help explain the extra-pancreatic effects of glibenclamide and possibly of other sulphonylurea drugs.