Effect of cyclic AMP, db-cyclic AMP and phosphodiesterase inhibitors on histamine inhibition of the contractile response of the mouse vas deferens

Abstract

Histamine inhibited the contractile response of the mouse vas deferens to various frequencies of stimulation, and the inhibition was inversely related to the frequency of stimulation. This effect of histamine was mimicked by cyclic AMP, db-cyclic AMP and various phosphodiesterase inhibitors (IBMX, aminophylline and theophylline). Histamine-produced inhibition, but not that produced by the other compounds, was blocked by cimetidine. The low concentrations (10-100 microM) of various phosphodiesterase inhibitors caused inhibition but failed to potentiate the inhibitory response to histamine. The basal cyclic AMP levels of the tissues were unaffected at these concentrations of aminophylline. At higher concentrations (1 and 5 mM), however, aminophylline significantly elevated the basal cyclic AMP levels of the tissues and markedly inhibited the contractile response to various frequencies of stimulation but still failed to enhance or potentiate the inhibitory response to histamine. In fact, the inhibitory response to histamine at these concentrations of aminophylline was reduced. Based on these and earlier [3] findings, it is concluded that, although histamine increases the accumulation of cyclic AMP in the mouse vas deferens and although its inhibitory effect on the preparation can be mimicked by both the cyclic nucleotides and phosphodiesterase inhibitors, the involvement of cyclic AMP in the mediation of its inhibitory response is still unresolved.

Histamine Stimulates Progesterone Synthesis and Cyclic Adenosine 3′,5′-Monophosphate Accumulation in Isolated Preovulatory Rat Follicles

“…Hence, stimulation of the Hz-receptor is associated with enhanced levels of cyclic adenosine 3',5'-monophosphate (cAMP) during relaxation of the smooth musculature in guinea pig ileum and rabbit mesen teric artery [30], during stimulation of the heart [27], and when an increase in gastric acid secretion is stimulated [36]. In the urogenital tract, stimulation of the H 2-receptor inhib its the contractile response in the mouse vas deferens [40] and influences glomerular function of the human kidney [35] with cAMP as a possible intracellular messenger.In order to elucidate whether histamine might mimic the LH effect on the preovulatory follicle, the cAMP formation and progesterone synthesis of incubated and superfused follicles from immature PMSG-treated rats were investi gated in the present study. …”