Pharmacological evidence for two different purinoceptors mediating blood pressure in the isolated perfused kidney

Recently, new purinoceptor agonists like; for example, diadenosinepentaphos phate (Ap(5)A) have been identified as potent human vasoactive substances. Ap(5)A activates P-2X-receptors but it is still not clear which subtype is activated and if this subtype is involved in permanent control of blood pre ssure. The activation of various purinoceptor subtypes were studied by meas uring effects of nucleotides like Ap(5)A and alpha,beta-methylene ATP (alph a,beta-meATP) during continuous perfusion in a rat isolated perfused kidney . Permanent perfusion with Ap(5)A elicited a transient and sustained vasoco nstriction with both vasoconstrictions to be different: the transient vasoc onstriction can be elicited with concentrations greater than or equal to 10 nM, whereas the sustained vasoconstriction is observed with concentrations greater than or equal to 1 nM. Ap(5)A acts via the same receptors as alpha ,beta-meATP, shown by inhibition of Ap(5)A's vasoconstrictive effects by pe rmanent perfusion with alpha,beta-meATP. Pyridoxal-phosphate 6-azophenyl-2; 4-disulphonic acid (PPADS) (30 mu M), a highly selective P-2X-receptor anta gonist antagonized both the transient and the sustained vasoconstriction in duced by Ap(5)A. Taken together: the results of the agonist profile of Ap(5 )A and comparing its findings to literature, it can be shown that the trans ient but not the sustained vasoconstriction is mediated via the P-2X1-recep tor. The profile of the sustained vasoconstriction does not fit to any know n P-2X-receptors. We conclude a yet unidentified P-2X-receptor which may pl ay an important role in blood pressure control.