Roles for α1-adrenoceptors during contractions by electrical field stimulation in mouse vas deferens.

Abstract

We have investigated the relative roles of α1-adrenoceptors and purinoceptors in contractions to low and high frequency stimulation of the mouse vas deferens, in terms of the time course of responses. In separate experiments, isometric contractile responses were obtained to 10 pulses at 1 Hz and 40 pulses at 10 Hz. Responses to 1 Hz stimulation consisted of a series of discrete peaks. The α1A-adrenoceptor antagonist RS100329 (10–9M–10–7M) significantly reduced the response to the first pulse, the α1D-adrenoceptor antagonist BMY7378 (10–7M–10–6M) significantly reduced the response to the first two pulses, and the non-selective α1-adrenoceptor antagonist prazosin (10–8M) reduced the response to the first 4 pulses at 1 Hz. Responses to 10 Hz stimulation consisted of an early peak response and a maintained plateau response. RS100329 significantly reduced the peak response but did not significantly affect the plateau response. Prazosin, significantly reduced both the peak and plateau responses. The α1A-adrenoceptor antagonist RS17053 in high concentrations reduced mainly the plateau response leaving a clear early peak response. The plateau response of contraction was almost abolished by the purinoceptor antagonist suramin. These results suggest that there is a relatively minor early α1D-adrenoceptor and a larger early α1A-adrenoceptor component to stimulation-evoked contractions of mouse vas deferens, but the major α1-adrenoceptor component is revealed by prazosin to be α1B-adrenoceptor mediated. α1B-Adrenoceptor activation probably facilitates contractions mediated by other α1-adrenoceptors and by purinoceptors. These results suggest that combined non-selective α1-adrenoceptor blockade, particularly α1B-adrenoceptor blockade, in addition to P2X1-purinoceptor blockade is useful in reducing male fertility.