Prazosin has low potency at α1A-adrenoceptors and high potency at α1D-adrenoceptors in rat vas deferens

1. We have investigated α₁-adrenoceptor subtypes mediating contractions to noradrenaline in epididymal portions of rat vas deferens.
2. Contractions to noradrenaline were investigated in the absence or presence of the noradrenaline transporter blocker cocaine.
3. In the absence of cocaine, contractions to noradrenaline were potently antagonized by RS100329, but not by BMY7378, and so are mediated mainly by α_1A-adrenoceptors.
4. In the presence of cocaine, noradrenaline potency was increased, particularly in terms of low concentrations and phasic contractions. Contractions to low concentrations of noradrenaline in the presence of cocaine were resistant to RS100329 but potently antagonized by BMY7378, demonstrating that α_1D-adrenoceptors are additionally involved in contractions amplified by cocaine.
5. In the absence of cocaine, prazosin exhibited relatively low potency as an antagonist against the α_1A-adrenoceptor-mediated component to the response. In the presence of cocaine, prazosin exhibited higher potency against the α_1D-adrenoceptor-mediated component.
6. In conclusion, prazosin has previously unreported selectivity for α_1D- over α_1A-adrenoceptors in functional studies of rat vas deferens. Contractions of rat vas deferens are mediated by α_1A- and α_1D-adrenoceptors. The range of prazosin potencies and of receptor subtypes previously reported in rat vas deferens may be explained by the presence of these two subtypes.