Modulation of prostaglandin synthesis in mammalian sperm acrosome reaction.
Exogenous arachidonic acid induces the acrosome reaction and the production of the prostaglandins PGE2 and PGF2 alpha in bovine spermatozoa. Exogenous PGE2 also induces the acrosome reaction and PGF2 alpha synthesis. To understand better the role of PGE2 in the induction of PGF2 alpha synthesis through modulation of phospholipase A2, inhibitors of this enzyme were used. The effects of PGE2 were blocked by phospholipase A2 inhibitors and this inhibition was reversed by addition of arachidonic acid. These data indicate that PGE2 activates phospholipase A2 to produce arachidonic acid. To determine whether protein kinase C modulates phospholipase A2 activity in this process, staurosporin, an inhibitor of protein kinase C, was used. The effect of PGE2 on PGF2 alpha production is inhibited by staurosporin and this inhibition was reversed by addition of arachidonic acid indicating that protein kinase C is involved in phospholipase A2 activation. The effect of exogenous arachidonic acid or PGE2 on the acrosome reaction is blocked by lipoxygenase inhibitors but not by inhibitors of cyclo-oxygenase, indicating that lipoxygenase products are involved in the mechanism of the acrosome reaction. The presented data shed light on the cross-talk between cyclo-oxygenase and lipoxygenase and their involvement in the sperm acrosome reaction. It is suggested that cyclo-oxygenase products modulate the activity of lipoxygenase which is a key enzyme in the mechanism leading to the acrosome reaction. Stimulation of cyclo-oxygenase to synthesize PGE2 activates phospholipase A2 to release arachidonic acid which is the substrate for lipoxygenase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Breitbart
H
H
Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
Shalev
Y
Y
Marcus
S
S
Shemesh
M
M
D000177:Acrosome / Q000187:drug effects*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D019311:Staurosporine
D000470:Alkaloids; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D000001:Calcimycin; D009637:Masoprocol; D015237:Dinoprost; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D019311:Staurosporine; D015232:Dinoprostone