Effects of P2-receptor agonists on sympathetic neuroeffector transmission in the rat isolated anococcygeus muscle

Abstract

The effects of nicotinamide adenine dinucleotide phosphate (NADPH), alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP), L-beta,gamma-methylene adenosine 5'-triphosphate (L-beta,gamma-MeATP), 2-methylthio-adenosine 5'-triphosphate (MeSATP) and adenosine-5-O-(2'-thiodiphosphate) (ADPbetaS) were investigated on the contractions to electrical field stimulation in the rat anococcygeus muscle. Stimulation-induced contractions were not affected by L-beta,gamma-MeATP (3-100 microM) or MeSATP (3-100 microM), but were enhanced by NADPH (10-100 microM), alpha,beta-MeATP (3-30 microM) and ADPbetaS (3-10 microM) in a concentration-dependent manner, and the enhancements were antagonised by the P2-receptor antagonist suramin (100 microM). The enhancement produced by alpha,beta-MeATP (10 microM) and ADPbetaS (10 microM) was also antagonised by pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (10 microM) and reactive blue 2 (100 microM). The enhancement produced by alpha,beta-MeATP (10 microM) was not altered by NG-nitro-L-arginine methyl ester (100 microM), desipramine (1 microM) or idazoxan (0.1 microM) excluding, respectively, the possible involvement of nitric oxide, neuronal amine uptake or alpha2-autoinhibition of noradrenergic transmission. Contractions elicited by low (0.1 and 0.3 microM) but not by higher (1 and 3 microM) concentrations of exogenously applied noradrenaline were enhanced by alpha,beta-MeATP (10 microM). Neither the resting nor the stimulation-induced effluxes of radioactivity from [3H]-noradrenaline-labelled anococcygeus muscles were affected by alpha,beta-MeATP (10-100 microM). The findings suggest that P2-receptors subserve the enhancing actions of NADPH, alpha,beta-MeATP and ADPbetaS on sympathetic neuroeffector transmission; however, the subtype of P2-receptor involved and its location remain unclear.