Adenosine A(2A) receptor-mediated facilitation of noradrenaline release involves protein kinase C activation and attenuation of presynaptic inhibitory receptor-mediated effects in the rat vas deferens

Abstract

In the epididymal portion of rat vas deferens, facilitation of noradrenaline release mediated by adenosine A(2A) receptors, but not that mediated by beta(2)-adrenoceptors or by direct activation of adenylyl cyclase, was attenuated by blockade of alpha(2)-adrenoceptors and abolished by simultaneous blockade of alpha(2)-adrenoceptors, adenosine A(1) and P2Y receptors. The adenosine A(2A) receptor-mediated facilitation was not changed by inhibitors of protein kinase A, protein kinase G or calmodulin kinase II but was prevented by inhibition of protein kinase C with chelerythrine or bisindolylmaleimide XI. Activation of protein kinase C with phorbol 12-myristate 13-acetate caused a facilitation of noradrenaline release that was abolished by bisindolylmaleimide XI and reduced by antagonists of alpha(2)-adrenoceptors, adenosine A(1) and P2Y receptors. Activation of adenosine A(2A) receptors attenuated the inhibition of noradrenaline release mediated by the presynaptic inhibitory receptors. This effect was mimicked by phorbol 12-myristate 13-acetate and prevented by bisindolylmaleimide XI. It is concluded that adenosine A(2A) receptors facilitate noradrenaline release by a mechanism that involves a protein kinase C-mediated attenuation of effects mediated by presynaptic inhibitory receptors, namely alpha(2)-adrenoceptors, adenosine A(1) and P2Y receptors.