Roles for α(1)-adrenoceptors during contractions by electrical field stimulation in mouse vas deferens

We have investigated the relative roles of α(1)-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 α(1A)-adrenoceptor antagonist RS100329 (10(–9)M–10(–7)M) significantly reduced the response to the first pulse, the α(1D)-adrenoceptor antagonist BMY7378 (10(–7)M–10(–6)M) significantly reduced the response to the first two pulses, and the non-selective α(1)-adrenoceptor antagonist prazosin (10(–8)M) 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 α(1A)-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 α(1D)-adrenoceptor and a larger early α(1A)-adrenoceptor component to stimulation-evoked contractions of mouse vas deferens, but the major α(1)-adrenoceptor component is revealed by prazosin to be α(1B)-adrenoceptor mediated. α(1B)-Adrenoceptor activation probably facilitates contractions mediated by other α(1)-adrenoceptors and by purinoceptors. These results suggest that combined non-selective α(1)-adrenoceptor blockade, particularly α(1B)-adrenoceptor blockade, in addition to P2X1-purinoceptor blockade is useful in reducing male fertility.