THE EFFECTS OF THEOPHYLLINE, DIAZOXIDE AND IMIDAZOLE ON ISOPROTERENOL-INDUCED INHIBITION OF THE RABBIT ILEUM

¹ Department of Pharmacology, University of Texas Medical Branch, Galveston, Texas

Theophylline and diazoxide have been reported to produce an inhibition of the phosphodiesterase that converts cyclic 3', 5'-adenosine monophosphate (cyclic 3', 5'-AMP) to 5'-AMP. Imidazole has been reported to enhance the ability of phosphodiesterase to break down cyclic 3', 5'-AMP. We have determined the effects of these agents on the inhibitory responses to isoproterenol and phenylephrine in the spontaneously contracting isolated rabbit ileum. The log dose-response curve for the inhibitory effect of isoproterenol was shifted to the left in the presence of 100µg/ml of theophylline (5 x 10^-4 M) and in the presence of 30 µg/ml of diazoxide (13 x 10^-4 M). Dose-response curves to isoproterenol obtained after removal of theophylline or diazoxide from the bath were shifted back to the right and did not differ significantly from the first control. The dose-response curve to isoproterenol was shifted to the right in the presence of imidazole, 10 µg/ml (1.5 x 10^-4 M), and then back to control after removal of imidazole. The dose-response curves for the inhibitory effect of phenylephrine were not altered by similar treatment with theophylline, diazoxide or imidazole. The effects of these agents on the inhibitory response to isoproterenol in the rabbit ileum are compatible with the view that cyclic 3', 5'-AMP mediates this beta receptor response in the rabbit ileum. We also conclude that cyclic 3', 5'-AMP is not involved in the intestinal inhibitory response due to alpha receptor activation.