Selectivity of diadenosine polyphosphates for rat P2X receptor subunits

The pharmacological activity of diadenosine polyphosphates was investigated at three recombinant P2X receptors (rat P2X(1), rat P2X(3), rat P2X(4)) expressed in Xenopus oocytes and studied under voltage-clamp conditions. For the rat P2X(1) receptor, only P-1,P-6-diadenosine hexaphosphate (Ap(6)A) was a full agonist yet 2-3 folds less potent than ATP. At rat P2X(3), P-1,P-4-diadenosine tetraphosphate (Ap(4)A), P-1,P-5-diadenosine pentaphosphate (Ap(5)A) and Ap(6)A were full agonists and more potent than ATP. Ap(4)A alone was equipotent with ATP at rat P2X(4), but only as a partial agonist. Compared to known data for rat P2X(2) and human P2X(1) receptors, our findings contrast with rat P2X(2) where only Ap(4)A is a full agonist although four folds less potent than ATP. At rat and human orthologues of P2X(1), Ap(5)A was a partial agonist with similar potency. These data provide a useful basis for selective agonists of P2X receptor subunits. (C) 1999 Elsevier Science B.V. All rights reserved.