title: Mastoparan elicits prostaglandin E2 generation and inhibits inositol phosphate accumulation via different mechanisms in rabbit astrocytes.
abstract: The effects of mastoparan on phosphoinositide hydrolysis and prostaglandin E2 (PGE2) generation were investigated in astrocytes cultured from rabbit brain. Mastoparan inhibited the accumulations of [3H]inositol phosphates induced by bradykinin (1 microM) in a time- and concentration-dependent manner. Mastoparan (3-30 microM) also released PGE2 in a time- and concentration-dependent manner. Mastoparan-induced release of PGE2 was inhibited by indomethacin, a cyclooxygenase inhibitor, by dexamethasone, a steroidal anti-inflammatory drug, and by pertussis toxin, an inactivator of some G proteins, such as Gi and Go. Mastoparan also caused [3H]arachidonic acid liberation, which was inhibited by dexamethasone or pertussis toxin. In contrast, indomethacin, dexamethasone and pertussis toxin failed to attenuate mastoparan-induced inhibition of [3H]inositol phosphate accumulation induced by bradykinin. Thus, mastoparan-induced inhibition of phosphoinositide hydrolysis does not involve pertussis toxin-sensitive G protein nor arachidonic acid metabolites. In addition to the inhibition of phospholipase C, mastoparan activates phospholipase A2 through pertussis toxin-sensitive G protein.
authors.affiliation: Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nakahata
authors.forename: K
authors.initials: K
authors.lastname: Imata
authors.forename: T
authors.initials: T
authors.lastname: Okawa
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Ishimoto
authors.forename: T
authors.initials: T
authors.lastname: Ono
authors.forename: Y
authors.initials: Y
authors.lastname: Ohizumi
authors.forename: H
authors.initials: H
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000032:analysis; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011817:Rabbits; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014862:Wasp Venoms / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D007295:Inositol Phosphates; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; D016718:Arachidonic Acid; C037500:mastoparan; D003907:Dexamethasone; D037342:Pertussis Toxin; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D015232:Dinoprostone; D007213:Indomethacin