Melittin stimulates phosphoinositide hydrolysis and placental lactogen release: arachidonic acid as a link between phospholipase A2 and phospholipase C signal-transduction pathways.
Previous investigations from this laboratory have implicated both phospholipase A2 and phospholipase C in the regulation of human placental lactogen release from human trophoblast. To study further the role of endogenous phospholipase A2 and the relationship between phospholipase A2 activation and phosphoinositide metabolism, we examined hPL and [3H]-inositol release from trophoblast cells in response to agents that stimulate or inhibit the endogenous enzyme. Melittin (0.5-2.0 micrograms/ml) stimulated rapid, dose-dependent, and reversible increases in the release of hPL, prostaglandin E, and [3H]-inositol. Mepacrine (0.1-0.25 mM) inhibited this stimulation. However, mepacrine had no effect on the stimulation of hPL and [3H]-inositol release by exogenous arachidonic acid (AA). These results indicate that the stimulation by melittin of phosphoinositide metabolism and hPL release is mediated by initial activation of phospholipase A2. Furthermore, the results support the possibility that AA, released as a consequence of phospholipase A2 activation, can act as a second messenger linking the two phospholipase pathways.
Zeitler
P
P
Department of Pediatrics, University of Cincinnati College of Medicine, OH.
Wu
Y Q
YQ
Handwerger
S
S
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D008555:Melitten / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010928:Placental Lactogen / Q000378:metabolism*; D011247:Pregnancy; D011458:Prostaglandins E / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*
D001095:Arachidonic Acids; D010716:Phosphatidylinositols; D011458:Prostaglandins E; D008555:Melitten; D016718:Arachidonic Acid; D007294:Inositol; D010928:Placental Lactogen; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases