Abstract

The present study investigates the possibility that with some agonists opposing and simultaneously occurring phenomena-contraction-induced increased responsiveness and receptor desensitization in part determine the magnitude of response of the rabbit ear artery. It has previously been shown that prior contraction of rabbit ear artery by equieffective histamine, KCl or serotonin concentrations increased norepinephrine (NE) responsiveness. However, the increased NE responsiveness that resulted from prior serotonin-induced contraction was less than that from histamine or KCl. In the present study, serotonin exposure in the presence of NaNO2 or papaverine concentrations that prevent smooth muscle contraction induced subsequent decreased NE responsiveness. This decreased responsiveness was reversed by KCl in the presence or absence of verapamil, but not by histamine. Ear arteries were everted in order to separate clearly the two phases of agonist-induced contraction. Everted vessels exposed to serotonin in the presence of NaNO2 subsequently responded to NE with initial transient contractions identical to those of controls, however, the secondary plateau contractions were reduced. Vessels exposed to NE or serotonin in the presence of NaNO2 or papaverine did not induce subsequent decreased norepinephrine and serotonin responsiveness, respectively. The present results suggest that prior contraction by serotonin induced increased responsiveness which masked underlying alpha adrenoceptor desensitization. Furthermore, the desensitization can be reversed by membrane depolarization.