Modeling P2Y receptor-Ca2+ response coupling in taste cells

摘要

Here we elaborated an analytical approach for the simulation of dose-response curves mediated by cellular receptors coupled to PLC and Ca2+ mobilization. Based on a mathematical model of purinergic Ca2+ signaling in taste cells, the analysis of taste cells responsiveness to nucleotides was carried out. Consistently with the expression of P2Y(2) and P2Y(4) receptors in taste cells, saturating ATP and UTP equipotently mobilized intracellular Ca2+. Cellular responses versus concentration of BzATP, a P2Y(2) agonist and a P2Y(4) antagonist, implicated high and low affinity BzATP receptors. Suramin modified the BzATP dose-response curve in a manner that suggested the low affinity receptor to be weakly sensitive to this P2Y antagonist. Given that solely P2Y(2) and P2Y(11) are BzATP receptors, their high sensitivity to suramin is poorly consistent with the suramin effects on BzATP responses. We simulated a variety of dose-response curves for different P2Y receptor sets and found that the appropriate fit of the overall pharmacological data was achievable only with dimeric receptors modeled as P2Y(2)/P2Y(4) homo- and heterodimers. Our computations and analytical analysis of experimental dose-response curves raise the possibility that ATP responsiveness of mouse taste cells is mediated by P2Y(2) and P2Y(4) receptors operative mostly in the dimeric form. (c) 2007 Elsevier B.V. All rights reserved.