Functional characterization of P2Y and P2X receptors in human eosinophils

Activation of purinoceptor by ATP induces in eosinophils various cell respo nses including calcium transients, actin polymerization, production of reac tive oxygen metabolites, CD11b-expression, and chemotaxis. Here, the effect of ion channel-gated P2X and/or G protein-coupled P2Y receptor agonists AT P, ATP gammaS, alpha,beta -meATP, 2-MeSATP, BzATP, ADP, CTP, and UTP on the intracellular Ca2+-mobilization, actin polymerization, production of react ive oxygen metabolites, CD11b expression and chemotaxis of human eosinophil s were measured and the biological activity was analyzed. Although all test ed nucleotides were able to induce al I these cell responses, the biologica l activity of the analyzed nucleotides were distinct. Agonists of the G pro tein-coupled P2Y receptors such as 2-MeSATP, UTP, and ADP have a higher bio logical activity for production of reactive oxygen metabolites, actin polym erization and chemotaxis in comparison to the ion channel-gated P2X agonist s alpha,beta -meATP, BzATP, and CTP. In contrast, P2Y and P2X agonist showe d similar potencies in respect to intracellular calcium transient and CD11b up-regulation. This conclusion was further supported by experiments with r eceptor iso-type antagonist KN62, EGTA or with the G(1) protein-inactivatin g pertussis toxin. These findings indicate participation of different purin orecptors in the regulation of cell responses in eosinophils.