Cyclic nucleotide levels in incubations of guinea pig trachea.

Abstract

Abstract The effects of several hormones and drugs on cyclic AMP and cyclic GMP levels in incubations of guinea pig tracheal rings were examined in order to compare alterations in cyclic nucleotide levels with inotropic effects of these agents reported by others. In general we observed that agents which can relax tracheal smooth muscle increased the levels of cyclic AMP and agents which can produce contraction increased the levels of cyclic GMP. However, several exceptions to these generalizations were observed. Epinephrine and prostaglandin E1 produced dose dependant increases in cyclic AMP levels which reached a peak in several minutes. The effect of epinephrine was prevented with the beta blocker propranolol and was unaltered by the alpha blocker phenoxybenzamine. The effect of epinephrine was additive to the stimulatory effect of the cyclic nucleotide phosphodiesterase inhibitor theophylline. Epinephrine and prostaglandin E1 had no effect on cyclic GMP levels. Surprisingly, acetylcholine and carbachol also increased cyclic AMP levels; however, these effects were prevented with either atropine or propranolol suggesting they were secondary to catecholamine release. Choline esters, histamine and theophylline also increased cyclic GMP levels. The effect of choline esters was prevented with atropine. The effect of histamine was blocked with either atropine or diphenhydramine which suggested that histamine released acetylcholine. Serotonin, angiotensin II and adrenocorticotrophin (ACTH) had no effects on cyclic AMP. Prostaglandin F2 α had no effect on cyclic AMP or cyclic GMP. These observations support the hypothesis that increased cyclic AMP is associated with relaxation and increased cyclic GMP with contraction of tracheal smooth muscle. Since contractility was not examined in this study and because of the cellular heterogeneity of the preparations used, additional studies are needed to examine this hypothesis more directly.