Nucleotide-evoked relaxation of rat vas deferens - a possible role for endogenous ATP released upon alpha(1)-adrenoceptor stimulation

The possibility was tested that endogenous ATP released upon alpha (1)-adre noceptor activation causes relaxation of the rat vas deferens smooth muscle . ATP, 2-methylthio ATP and adenosine relaxed the vas deferens precontracte d 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 t o ATP. The P2 receptor antagonist reactive blue 2 markedly reduced the rela xation (by up to 73 %); suramin, pyridoxalphosphate-6-azophenyl-2 ' ,4 ' -d isulphonic acid (PPADS) and acid blue 129 caused no change. ATP, but not (a lpha,beta -MeATP, also attenuated contractions elicited by noradrenaline at resting tension; reactive blue 2 blocked the inhibitory effect of ATP. Rea ctive blue 2, by itself, enhanced the response to noradrenaline (by up to 3 6%); suramin, PPADS and acid blue 129 caused no change. In the presence of the ATP-degrading enzymes apyrase and nucleotide pyrophosphatase, the facil itatory effect of reactive blue 2 was lost. Apyrase, by itself, enhanced th e response to noradrenaline (by 13%). The results indicate that endogenous ATP. released from rat vas deferens smooth muscle upon alpha (1)-adrenocept or stimulation, causes relaxation. The site of action of ATP is not a typic al smooth muscle P2Y receptor. (C) 2001 Elsevier Science B.V. All rights re served.