title: Effects of ATP on phosphoinositide hydrolysis and prostaglandin E2 generation in rabbit astrocytes.
abstract: Extracellular ATP secreted from stimulated nerves plays a role in neurotransmission. This study examined the effects of extracellular ATP on phospholipase A2 and C signalling pathways in rabbit astrocytes. ATP caused prostaglandin E2 (PGE2) generation and phosphoinositide hydrolysis in a time- and concentration-dependent manner. A P2y purinoceptor-selective agonist, 2-methylthio-ATP also caused phosphoinositide hydrolysis, but not PGE2 generation. A P2x purinoceptor-selective agonist, alpha, beta-methylene-ATP did not cause either phosphoinositide hydrolysis or PGE2 generation. Although pertussis toxin had no effect on 2-methylthio-ATP-induced phosphoinositide hydrolysis, it markedly decreased ATP-induced PGE2 generation, with significant inhibition of phosphoinositide hydrolysis. Dexamethasone and indomethacin which potently inhibited ATP-induced PGE2 generation, caused partial inhibition of phosphoinositide hydrolysis, suggesting that pertussis toxin-sensitive component of ATP-induced phospholipase C activation is mediated by cyclo-oxygenase metabolites of arachidonic acid. These results suggest that a stimulation of P2y receptor results in phospholipase C activation in a pertussis toxin-insensitive manner, and that a P2 receptor other than the P2y or P2x subtypes is involved in ATP-induced phospholipase A2 activation via a pertussis toxin-sensitive G protein.
authors.affiliation: Department of Pharmacology, Fukushima Medical College, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishimoto
authors.forename: N
authors.initials: N
authors.lastname: Nakahata
authors.forename: I
authors.initials: I
authors.lastname: Matsuoka
authors.forename: H
authors.initials: H
authors.lastname: Nakanishi
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D006868:Hydrolysis; D007213:Indomethacin / Q000494:pharmacology; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D058910:Purinergic P2 Receptor Agonists; D011817:Rabbits; D018048:Receptors, Purinergic P2 / Q000145:classification / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010716:Phosphatidylinositols; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D015232:Dinoprostone; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D007213:Indomethacin; C008501:2-methylthio-ATP