VASOCONSTRICTOR RESPONSES TO THE P-2X-PURINOCEPTOR AGONIST BETA,GAMMA-METHYLENE-L-ATP IN HUMAN CUTANEOUS AND RENAL BLOOD-VESSELS

1 Strips of human saphenous veins and of human renal arteries and vein s were superfused with Krebs-Henseleit solution at 37 degrees C. Const rictor responses were elicited by exogenous noradrenaline and the P-2X -purinoceptor-selective agonist, beta,gamma-methylene-L-ATP. 2 In huma n saphenous veins, beta,gamma-methylene-L-ATP (0.3-3G mu M; EC(50) 2.2 mu M) induced marked constrictor responses. The maximal response to b eta,gamma-methylene-L-ATP was similar to the maximal response to norad renaline. The P-2-purinoceptor antagonist suramin (30 mu M) shifted th e concentration-response curve of beta,gamma-methylene-L-ATP to the ri ght (apparent pK(B) value 4.8); suramin (100 mu M) markedly inhibited the responses to beta,gamma-methylene-L-ATP. The preferential P-2X-pur inoceptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphoni c acid (PPADS; 3 mu M) slightly reduced the response to beta,gamma-met hylene-L-ATP. At a ten times higher concentration (30 mu M), PPADS alm ost abolished the responses to beta,gamma-methylene-L-ATP. PPADS (30 m u M), in contrast, caused no significant change in the concentration-r esponse curve of noradrenaline. 3 In extrarenal and intrarenal arterie s, EC(50) values and maximal responses to noradrenaline were similar w hen compared with responses to noradrenaline in saphenous veins. Norad renaline also constricted extrarenal veins. However, in contrast to th e results obtained on saphenous veins, beta,gamma-methylene-L-ATP caus ed almost no constrictor responses in extrarenal veins and arteries an d only moderate responses in intrarenal arteries. 4 The results demons trate marked differences in responsiveness of human blood vessels to t he selective P-2X-purinoceptor agonist, beta,gamma-methylene-L-ATP, su ggesting tissue differences in the occurrence or operation of P-2X-pur inoceptors in human vascular tissues. Moreover, the results indicate t hat PPADS blocks P-2X-purinoceptors in human isolated blood vessels as previously demonstrated in animal blood vessels.