Relaxant effects of forskolin in smooth muscle. Role of cyclic AMP

Abstract

Forskolin was found to cause concentration dependent, reversible relaxations of isolated smooth muscle preparations including rat aorta, bovine coronary artery, canine coronary artery, guinea pig taenia caeci and rabbit small intestine. The relaxant effects of forskolin in guinea pig taenia caeci and rabbit small intestine were potentiated by cyclic nucleotide phosphodiesterase inhibitors Ro 20-1724 and MIX. In rabbit small intestine, Ro 20-1724 also potentiated the relaxant effects of isoproterenol but not those of verapamil or 2-chloroadenosine. However, in bovine coronary arteries the phosphodiesterase inhibitors had to be used at concentrations of 100 nM or below because of relaxant effects and did not alter forskolin-induced relaxations. Forskolin caused a concentration dependent activation of adenylate cyclase in broken cell preparations from guinea pig taenia caeci and rabbit small intestine, exceeding the stimulatory effect of 10 mM NaF. These results indicate that relaxations of smooth muscle by forskolin are mediated by cyclic AMP and, in turn, that cyclic AMP may well serve as an intracellular mediator of physiological relaxant stimuli.