Grandordy_1987_Life.Sci_41_1621

Hydrolysis of membrane inositol phospholipids during agonist-induced contraction in bronchial smooth muscle leads to formation of inositol phosphates. Inositol phosphates are associated with intracellular Ca++ mobilization, which in smooth muscle leads to contraction. We have investigated the effects of inhibitors of the contraction, theophylline, isoproterenol (isoprenaline), and verapamil, on contraction due to carbachol and histamine in bovine airway smooth muscle, and on the formation of inositol phosphates in the same preparation. Since phospholipase C and A2 are involved in the formation of inositol phosphates, we have also studied the effect of inhibitors of phospholipases, dexamethasone and mepacrine, on the accumulation of inositol phosphates. Theophylline, isoproterenol and verapamil elicited a concentration-dependent relaxation of pre-contracted smooth muscle, with the following order of potency: Isoproterenol greater than verapamil greater than theophylline. The relaxant effect was more effective on histamine than on carbachol-induced contraction and depended on the initial airway tone. However, neither theophylline, isoproterenol or verapamil, nor dexamethasone or mepacrine changed the basal level of inositol phosphates or affected the rise due to agonists. We conclude that the smooth muscle effects of theophylline, isoproterenol, verapamil, dexamethasone and mepacrine are not mediated by interference with membrane phosphoinositide breakdown.