Aalpha,beta-methylene ATP enhances P2Y4 contraction of rabbit basilar artery

Interactions between different selective P2 receptor agonists have been used as tools to identify different P2 receptor subtypes. In the present study, we examined the P2 receptor subtypes and the mechanisms of potentiation of UTP contraction (P2Y contraction) by alpha,beta-methylene ATP [(2-carboxypiperazin-4-yl)propyl-1-phosphanoic acid (CPP), a P2X agonist] using isometric tension in the denuded rabbit basilar artery. We made the following observations: 1). a predominant P2X receptor contraction was observed in the rabbit ear artery by the rank order of CPP >> 2-methylthioATP > ATP > UTP; 2). functional P2Y receptors were observed in the rabbit basilar artery by the rank order of UTP >> ATP = CPP = 2-methylthioATP; 3). CPP potentiated UTP-, ATP-, and ATPgammaS-induced contractions, possibly by activation of P2Y4 receptors because ATPgammaS does not activate P2Y6 receptors; and 4). ectonucleotidase did not play a predominant role in the potentiative effect of CPP because Evans blue, Ca(2+)-free medium, or divalent cation Ni(2+) did not affect the effect of CPP. Evans blue potentiated the contraction by UTP but not by ATP or ATPgammaS. We conclude that CPP enhanced P2Y4-mediated contraction in the rabbit basilar artery, and the influence by ectonucleotidases on CPP-potentiation remains unclear.