Interaction between adenosine A(2B)-receptors and alpha(2)-adrenoceptors on the modulation of noradrenaline release in the rat vas deferens: Possible involvement of a group 2 adenylyl cyclase isoform

Abstract

In the prostatic portion of rat vas deferens, activation of adenosine A(2B)-receptors, beta(2)-adrenoceptors, adenylyl cyclase or protein kinase A caused a facilitation of noradrenaline release. Blockade of alpha(2)-adrenoceptors with yohimbine (1 mu M) attenuated the facilitation mediated by adenosine A(2B)-receptors and by direct activation of adenylyl cyclase with forskolin but not that mediated by beta(2)-adrenoceptors or by direct activation of protein kinase A with 8-bromoadenosine-3,5'-cyclicAMP. The adenosine A(2B)- and the beta(2)-adrenoceptor-mediated facilitation was prevented by the adenylyl cyclase inhibitors, 2',5'-dideoxyadenosine (3 mu M) and 9-cyclopentyladenine (100 mu M), at concentrations that also attenuated the release enhancing effect of forskolin, but were not changed by the phospholipase C inhibitor 1-[6-[((17 beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U-73122, 1 mu M). Facilitation of noradrenaline release mediated by adenosine A-B-receptors was also attenuated by activation of protein kinase C with the phorbol ester 12-myristate 13-acetate (1 mu M) and by inhibition of G beta gamma subunits with an anti-beta gamma peptide; facilitation mediated by beta(2)-adrenoceptors was mainly attenuated by the calmodulin inhibitor calmidazolium (10 mu M) and by the calmodulin kinase II inhibitor (N-[2-[N-(4-chlorocinnamyl)-N-methylaminomethyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzene-sulfonamide phosphate (KN-93, 5 mu M). The results suggest that adenosine A(2B)- but not beta(2)-adrenoceptor-mediated facilitation of noradrenaline release is enhanced by an ongoing activation of alpha(2)-adrenoceptors. They further suggest that adenosine A(2B)-receptors and beta(2)-adrenoceptors are coupled to distinct adenylyl cyclase isoforms what may explain the different influence of alpha(2)-adrenoceptor signalling pathway on the facilitatory effects mediated by the two adenylyl cyclase coupled receptors.