Interaction between adenosine A 2B-receptors and α 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, β 2-adrenoceptors, adenylyl cyclase or protein kinase A caused a facilitation of noradrenaline release. Blockade of α 2-adrenoceptors with yohimbine (1 μM) attenuated the facilitation mediated by adenosine A 2B-receptors and by direct activation of adenylyl cyclase with forskolin but not that mediated by β 2-adrenoceptors or by direct activation of protein kinase A with 8-bromoadenosine-3′,5′-cyclicAMP. The adenosine A 2B- and the β 2-adrenoceptor-mediated facilitation was prevented by the adenylyl cyclase inhibitors, 2′,5′-dideoxy-adenosine (3 μM) and 9-cyclopentyladenine (100 μM), at concentrations that also attenuated the release enhancing effect of forskolin, but were not changed by the phospholipase C inhibitor 1-[6-[((17β)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U-73122, 1 μM). Facilitation of noradrenaline release mediated by adenosine A 2B-receptors was also attenuated by activation of protein kinase C with the phorbol ester 12-myristate 13-acetate (1 μM) and by inhibition of Gβγ subunits with an anti-βγ peptide; facilitation mediated by β 2-adrenoceptors was mainly attenuated by the calmodulin inhibitor calmidazolium (10 μM) 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 μM). The results suggest that adenosine A 2B- but not β 2-adrenoceptor-mediated facilitation of noradrenaline release is enhanced by an ongoing activation of α 2-adrenoceptors. They further suggest that adenosine A 2B-receptors and β 2-adrenoceptors are coupled to distinct adenylyl cyclase isoforms what may explain the different influence of α 2-adrenoceptor signalling pathway on the facilitatory effects mediated by the two adenylyl cyclase coupled receptors.