Functional characterization of P2Y and P2X receptors in human eosinophils.
Activation of purinoceptor by ATP induces in eosinophils various cell responses including calcium transients, actin polymerization, production of reactive oxygen metabolites, CD11b-expression, and chemotaxis. Here, the effect of ion channel-gated P2X and/or G protein-coupled P2Y receptor agonists ATP, ATPgammaS, alpha,beta-meATP, 2-MeSATP, BzATP, ADP, CTP, and UTP on the intracellular Ca(2+)-mobilization, actin polymerization, production of reactive oxygen metabolites, CD11b expression and chemotaxis of human eosinophils were measured and the biological activity was analyzed. Although all tested nucleotides were able to induce all these cell responses, the biological activity of the analyzed nucleotides were distinct. Agonists of the G protein-coupled P2Y receptors such as 2-MeSATP, UTP, and ADP have a higher biological activity for production of reactive oxygen metabolites, actin polymerization and chemotaxis in comparison to the ion channel-gated P2X agonists alphabeta-meATP, BzATP, and CTP. In contrast, P2Y and P2X agonist showed similar potencies in respect to intracellular calcium transient and CD11b up-regulation. This conclusion was further supported by experiments with receptor iso-type antagonist KN62, EGTA or with the G(i) protein-inactivating pertussis toxin. These findings indicate participation of different purinorecptors in the regulation of cell responses in eosinophils.
Idzko
M
M
Department of Pneumology, University of Freiburg, Germany.
Dichmann
S
S
Panther
E
E
Ferrari
D
D
Herouy
Y
Y
Virchow
C
C
Luttmann
W
W
Di Virgilio
F
F
Norgauer
J
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009711:Nucleotides / Q000494:pharmacology; D037342:Pertussis Toxin; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000145:classification / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000199:Actins; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D016177:Macrophage-1 Antigen; D009711:Nucleotides; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D010566:Virulence Factors, Bordetella; D004533:Egtazic Acid; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D037342:Pertussis Toxin; D002118:Calcium