ATP activates the potassium channel and enhances cytosolic Ca2+ release via a P2Y purinoceptor linked to pertussis toxin-insensitive G-protein in brain artery endothelial cells.
ATP produced whole-cell potassium currents in cultured endothelial cells of the bovine brain cortical arteries. P2 purinoceptor agonists evoked similar currents with the order of their potency: 2-methylthio ATP > ATP >> alpha, beta-methylene ATP > or = UTP > or = ADP >> AMP. ATP-evoked currents were inhibited by GDP beta S, but not by pertussis toxin (PTX). Furthermore, a phospholipase C (PLC) inhibitor, protein kinase C inhibitor, or cAMP-dependent protein kinase inhibitor had no effect on the currents. In addition to these effects, ATP enhanced intracellular free Ca2+ concentration ([Ca2+]i) in the presence and absence of extracellular Ca2+, and this [Ca2+]i increase was not inhibited by a PLC inhibitor. These results, thus, provide an indication that ATP activates the potassium channel and enhances [Ca2+]i via a P2Y purinoceptor linked to a PTX-insensitive G-protein, which is not involved in a PLC-mediated signaling pathway.
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002536:Cerebral Arteries; D002540:Cerebral Cortex / Q000098:blood supply; D003600:Cytosol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009355:Neomycin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014544:Uridine Triphosphate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000227:Adenine Nucleotides; D015221:Potassium Channels; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D010566:Virulence Factors, Bordetella; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009355:Neomycin; D002118:Calcium; D014544:Uridine Triphosphate