Investigation of postjunctional α1- and α2-adrenoceptor subtypes in vas deferens from wild-type and α2A/D-adrenoceptor knockout mice

1 The subtypes of alpha(1)- and alpha(2)-adrenoceptor mediating contractions of vas deferens have been examined in wild-type and alpha(2A/D)-adrenoceptor knockout mice. 2 Maximum contractions to noradrenaline but not phenylephrine were significantly greater in vas from wild-type. The alpha(1A)-adrenoceptor antagonist RS100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy)phenyl]-1-piperazinyl]propyll-2,4-(1H)-pyrimidinedione) (10 nm) significantly shifted the potency of noradrenaline. The alpha(2D)-adrenoceptor antagonist BRL 44408 (2-[4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole) significantly reduced the maximum contraction to noradrenaline in wild-type but not in knockout. 3 Following prazosin (0.1 muM), a component of the contraction to noradrenaline in wild-type but not in knockout was sensitive to the a2-adrenoceptor antagonist yohimbine. 4 Nifedipine (10 pm) or suramin (100 pm) reduced the contraction to 10 Hz stimulation for 4 s to an early peak and small maintained response. The peak was abolished by the alpha(1)-adrenoceptor antagonist prazosin. 5 RS100329 or prazosin inhibited 10Hz stimulation evoked contractions with a U-shaped concentration-response curve: inhibiting responses up to 0.1 mum, with a reversal of inhibition above this concentration. In the presence of suramin or nifedipine, the reversal of inhibition by high concentrations of prazosin was reduced. 6 The alpha(1D)-adrenoceptor selective antagonist BMY7378 (8-[2-(4-(2- methoxyphenyl)piperazin-1-yl)ethyl]-8-azaspiro[4,5]decane-7,9-dione) produced inhibition of 10 Hz evoked contractions only in high concentrations. 7 In conclusion, contractions to nerve stimulation in mouse vas deferens involve largely alpha(1D)-adrenoceptors and purmoceptors. alpha(1)-Adrenoceptor antagonists in high concentrations increase the purinergic response presumably by blocking prejunctional alpha(2)-adrenoceptor-mediated inhibition. In the presence of nifedipine, responses are predominantly alpha(1)-adrenoceptor mediated. Contractions to exogenous noradrenaline involved both alpha(1A)- and alpha(2A/D)-adrenoceptors in wild-type mice. British Journal of Pharmacology (2003) 138, 1069-1076. doi: 10. 1038/sj.bjp.705137.