A P2X purinoceptor cDNA conferring a novel pharmacological profile

Abstract

We have cloned P2X4, a member of the P2-purinoceptor family, which has a new pharmacological profile. Rat P2X4 is distantly related to P2X1, P2X2 and P2X3 and is expressed in brain, spinal cord, lung, thymus, bladder, adrenal, testis and vas deferens. This ligand gated ion channel is activated by ATP and analogs with the potency order of ATP > ATP gamma S > 2-methylthio ATP > ADP approximately alpha beta-methylene ATP. However, none of the currently used P2X purinoceptor antagonists suramin, reactive blue 2 and PPADS blocked ATP evoked currents; in contrast their application resulted in potentiation of the agonist response. Due to lack of any known antagonist for P2X4 it is unlikely that native P2X4 has previously been recognized as a P2X purinoceptor.