Mastoparan elicits prostaglandin E2 generation and inhibits inositol phosphate accumulation via different mechanisms in rabbit astrocytes.
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.
Nakahata
N
N
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Japan.
Imata
K
K
Okawa
T
T
Watanabe
Y
Y
Ishimoto
H
H
Ono
T
T
Ohizumi
Y
Y
Nakanishi
H
H
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*
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