The pharmacological activity of diadenosine polyphosphates was investigated
at three recombinant P2X receptors (rat P2X(1), rat P2X(3), rat P2X(4)) ex
pressed 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) wa
s 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 (A
p(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. Comp
ared 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 bas
is for selective agonists of P2X receptor subunits. (C) 1999 Elsevier Scien
ce B.V. All rights reserved.