Differential effects of diadenosine phosphates on purinoceptors in the rat isolated perfused kidney

The activation of various purinoceptors in rat renal vasculature by P 1 ,P 2 ‐diadenosine pyrophosphate (Ap 2 A), P 1 ,P 3 ‐diadenosine triphosphate (Ap 3 A), P 1 ,P 4 ‐diadenosine tetraphosphate (Ap 4 A), P 1 ,P 5 ‐diadenosine pentaphosphate (Ap 5 A), P 1 ,P 6 ‐diadenosine hexaphosphate (Ap 6 A) was studied by measuring their effects of perfusion pressure of a rat isolated perfused kidney. The vasoconstrictive response to Ap 5 A was completely due to P 2X purinoceptor activation, that to Ap 4 A and Ap 6 was P 2X purinoceptor mediated to a large extent, as evidenced by the inhibitory effects of suramin and pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid tetrasodium (PPADS). The vasoconstrictive effects of Ap 2 A and Ap 3 A were mostly due to stimulation of A 1 ‐receptors, as shown by the inhibitory effect of 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX). The vasoconstrictive response to Ap 6 A was partially insensitive to A 1 and P 2X purinoceptor blockers. In raised tone preparations Ap 2 A and Ap 3 A evoked vasodilatation, which was blocked by the A 2 receptor blocker, 3,7‐dimethyl‐1‐propargylxanthine (DMPX). In raised tone preparations Ap 4 A evoked vasodilatation when the P 2 ‐purinoceptors were blocked by suramin. The activation of different purinoceptor subtypes by diadenosine phosphates critically depends on the number of phosphate groups.British Journal of Pharmacology (1997) 120 , 1453–1460; doi: 10.1038/sj.bjp.0701074