Forskolin-induced elevation of rat jejunal cyclic AMP levels and stimulation of active glucose transport in vitro.

The adenylate cyclase stimulator forskolin enhanced both mucosal cyclic AMP levels and D-aldohexose transport in rat jejunum in vitro in a concentration-dependent manner. With mucosal cyclic AMP elevated to 400% of basal values, active D-glucose transport was at 200% of control values. Transport parameters, as determined in a three compartment model using a dual label method, indicate a) increased "uphill" glucose transport at the brush border membrane with higher intracellular accumulation, b) unchanged serosal to mucosal glucose fluxes and passive permeabilities. Transport stimulating effects of forskolin were also present with D-galactose in the rat. In mouse jejunum active transport of D-glucose and 3-O-methylglucose was increased by forskolin 10 mumol/l. Phlorizin inhibited D-glucose transport as well as L-glucose transport in the rat were not changed by the persisting cyclic AMP elevation induced by forskolin. The results show a positive correlation of active intestinal hexose transport with a modest elevation of mucosal cyclic AMP. In accordance to current models of cyclic AMP-induced changes in intestinal fluid absorption, rat jejunal net fluid transport was reduced by 40% with 20 mumol/l forskolin.