CALCITONIN-GENE-RELATED PEPTIDE SELECTIVELY INCREASES CAMP LEVELS IN THE GUINEA-PIG URETER

Calcitonin gene-related peptide (CGRP, 0.1 mu M) and forskolin (10 mu M) both produced a time-dependent accumulation of cAMP in homogenates of the guinea-pig ureter, while cromakalim (3 mu M) was ineffective. N either agent did increase the cGMP levels. cAMP accumulation induced b y CGRP or forskolin was unchanged by glibenclamide (1 mu M). In sucros e gap, the application of forskolin (1-10 mu M for 15 s) hyperpolarize d the smooth muscle membrane and its effect was greatly enhanced when tested in a low-K+ medium (extracellular K+ reduced from 5.9 to 1.2 mM ). The hyperpolarization produced by 10 mu M forskolin was reduced and abolished by 1 and 10 mu M glibenclamide, respectively, in both norma l and low-K+ medium. The present findings demonstrate that CGRP determ ines a selective cAMP accumulation in the guinea-pig ureter and sugges t that elevation of cAMP may be involved in the opening of glibenclami de-sensitive K+ channels in the ureter smooth muscle.