Further Studies of the Action of Cyclic Amp on the Electrical and Mechanical Activities of Intestinal Smooth Muscle

Abstract

Abstract-Effects of externally applied cyclic AMP and other adrenergic stimulants on the electrical and mechanical activities of the cat small intestine were observed by using pressure electrodes. The electrical and mechanical activities were suppressed by cyclic AMP and beta-stimulants.Those inhibitory actions of cyclic AMP and beta-stimulants were potentiated under the treatment with caffeine, theophylline and papaverine which inhibits the phosphodiesterase activity.On the other hand, the inhibitory action of cyclic AMP and beta-stimulants was decreased in imidazole, an agent that increases phosphodiesterase activity. Exogenous applied concanavalin A, an agent that inhibits the adenyl cyclase activity, showed no observable changes in both activities but the effects of beta-stimulants were decreased after treatment with con canavalin A. No obvious changes on both activities were obtained in cyclic GMP and dibutyryl cyclic GMP. These findings tentatively support the hypothesis that cyclic AMP is a second messenger in the inhibitory responses to beta-stimulants on the intestinal smooth muscle. However, it is also concluded that the inhibition of me chanical activity caused by cyclic AMP is partially due to suppression of the membrane activity.In relation to the relaxation mechanism of smooth muscles, several authors (1, 2, 3) have emphasized two subjects, that is, the activation of adenyl cyclase in cell membrane by beta-adrenergic stimulants and the increase of intracellular level of cyclic 3',5'-adenosine monophosphate (cyclic AMP). In previous papers (4, 5), it has been reported that cyclic AMP and dibutyryl cyclic AMP inhibited the spontaneous electrical and mechanical ac tivities of the intestinal smooth muscle. These actions of cyclic AMP and related compounds may thus possibly relate with adenyl cyclase and phosphodiesterase activity in the smooth muscle. On the other hand, it has been acknowledged that the phosphodiesterase activity is affected by externally applied caffeine (3), theophylline (3), papaverine (6, 7) and imidazole (3) and that adenyl cyclase activity is affected by concanavalin A (8).This report is concerned with the action of cyclic AMP on both activities of intestinal smooth muscle under affecting factors on the enzyme activity. MATERIALS AND METHODSThe small intestine was removed from adult cats which had been anesthetized with isor_ole. For the purpose of recording electrical and mechanical activities, a segment, 3 cm to 3.5 cm long, was slipped onto a rectangular Lucite holder and the holder was mounted in the normal solution at 36-37`-'C in a 200 nil Lucite chamber. One end of the segment was