Nucleotide-evoked relaxation of rat vas deferens -: a possible role for endogenous ATP released upon α1-adrenoceptor stimulation

The possibility was tested that endogenous ATP released upon alpha (1)-adrenoceptor activation causes relaxation of the rat vas deferens smooth muscle. ATP, 2-methylthio ATP and adenosine relaxed the vas deferens precontracted with 80 mM K+. The metabolically stable P2 receptor agonists alpha,beta -methylene ATP (alpha,beta -MeATP) and adenosine 5 ' -O-(2-thiodiphosphate) (ADP betaS) had little or no effect. The adenosine P1 receptor antagonist 8-(para-sulfophenyl)theophylline did not significantly affect the response to ATP. The P2 receptor antagonist reactive blue 2 markedly reduced the relaxation (by up to 73 %); suramin, pyridoxalphosphate-6-azophenyl-2 ' ,4 ' -disulphonic acid (PPADS) and acid blue 129 caused no change. ATP, but not (alpha,beta -MeATP, also attenuated contractions elicited by noradrenaline at resting tension; reactive blue 2 blocked the inhibitory effect of ATP. Reactive blue 2, by itself, enhanced the response to noradrenaline (by up to 36%); suramin, PPADS and acid blue 129 caused no change. In the presence of the ATP-degrading enzymes apyrase and nucleotide pyrophosphatase, the facilitatory effect of reactive blue 2 was lost. Apyrase, by itself, enhanced the response to noradrenaline (by 13%). The results indicate that endogenous ATP. released from rat vas deferens smooth muscle upon alpha (1)-adrenoceptor stimulation, causes relaxation. The site of action of ATP is not a typical smooth muscle P2Y receptor. (C) 2001 Elsevier Science B.V. All rights reserved.