DUAL CONTRACTILE EFFECTS OF ATP RELEASED BY FIELD STIMULATION REVEALED BY EFFECTS OF ALPHA,BETA-METHYLENE ATP AND SURAMIN IN RAT TAIL ARTERY

1 The field stimulation-induced release of endogenous ATP and noradren aline (NA) and contractile response in rat isolated tail artery were e xamined. The release of ATP was studied by extracellular electrophysio logical recording and that of NA by a novel voltammetrical technique. The effects of the P2-purinceptor antagonist, suramin, on these parame ters were compared with those of alpha,beta-methylene ATP, a P2x-purin oceptor desensitizing agent. 2 Neither alpha,beta-methylene ATP (10 mu m) nor suramin (100-500 mum) had significant effects on the extracellu larly recorded nerve terminal action potential but both abolished the ATP-induced excitatory junction current caused by stimulation at 0.1 H z. Neither agent affected significantly the voltammetrically measured release of NA induced by 10 or 100 pulses at 20 Hz. 3 Combined blockad e of both postjunctional alpha1- and alpha2-adrenoceptors by prazosin and yohimbine (both 0.1 mum) profoundly depressed the contractile resp onse to 10 pulses at 20 Hz. The small and fast residual contraction in the presence of these agents was abolished by alpha,beta-methylene AT P (10 mum) and inhibited by suramin in a concentration-dependent manne r (10-500 mum; IC50 75 mum) and was hence probably caused by ATP or a related nucleotide. 4 When added first, alpha,beta-methylene ATP (10 m um) or suramin (100-500 mum) delayed the onset and enhanced the amplit ude of the neurogenic contraction. This enhanced response was abolishe d by further addition of prazosin and yohimbine (both 0.1 mum). 5 The K+ channel blocker, tetraethylammonium (10mm), dramatically enhanced t he contractile response to 100 pulses at 1 Hz and caused it to become diphasic. Addition of alpha,beta-methylene ATP (10 mum) or suramin (10 0-500 mum) abolished the large initial twitch component of this contra ction and depressed the tonic phase. 6 Like alpha,beta-methylene ATP, suramin (500 mum) had no effect on the contraction caused by exogenous NA (10 nm - 100 mum) or KCl (60 mm); both agents almost abolished the contraction caused by ATP (100 mum). 7 In conclusion, (i) the contrac tile response of rat tail artery to electrical field stimulation is me diated by both ATP and NA, and is thus an expression of ATP-NA co-tran smission, (ii) the released ATP exerts two opposite effects via 'P2X-l ike' purinoceptors, triggering the initial rapid phase of the neurogen ic contraction and restricting the NA-mediated component of the contra ction; and (iii) the source and possible physiological role of the ATP which causes the inhibitory effect are unknown at present.