Myoblast fusion is regulated by a prostanoid of the one series independently of a rise in cyclic AMP.
The role of prostanoids in the regulation of chick myoblast differentiation has been investigated. At 3 X 10(-6) M, indomethacin and chloroquine specifically inhibit cell fusion. They do not affect cell proliferation, alignment, or the expression of two muscle-specific proteins, namely, the acetylcholine receptor and the muscle-specific form of creatine phosphokinase. The results demonstrate that it is indomethacin's activity as an inhibitor of prostaglandin synthesis at the cyclooxygenase step that causes the block of cell fusion, whereas chloroquine probably acts at the earlier step of phospholipase A. Prostaglandin E1 (PGE1), but not prostaglandin E2 (PGE2), rapidly reverses the inhibition of fusion imposed by indomethacin or chloroquine. The dose response of the myoblasts to PGE1 is a bell-shaped curve with a 100% reversal of fusion at approximately 10(-9) M. Eicosatrienoate and linoleate reverse the inhibition of fusion with similar kinetics, whereas arachidonate is completely ineffective. The ability of PGE1 and eicosatrienoate but not PGE2 and arachidonate to restore fusion to control levels implies that fusion is specifically regulated by a prostanoid of the one series. The reversal of the fusion-block by linoleate further suggests that this fatty acid provides the necessary source of eicosatrienoate in the myoblast plasma membrane. At 10(-8) M and above, PGE1 and PGE2 stimulate adenylate cyclase and depress control fusion as does 10(-5) M isoproterenol. The beta-adrenergic blocker propranolol abolishes both isoproterenol's inhibition of myoblast fusion and its activation of adenylate cyclase. The similar depressions imposed on cell fusion by 10(-8)-10(-6) M prostanoid and 10(-5) M isoproterenol suggest that in both cases the depressive effects are mediated by cyclic AMP. It is concluded that a prostanoid of the one series regulates fusion by a cyclic AMP-independent mechanisms.
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002459:Cell Fusion / Q000187:drug effects*; D002478:Cells, Cultured; D002642:Chick Embryo; D002738:Chloroquine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D004537:Eicosanoic Acids / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009132:Muscles / Q000166:cytology* / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology
D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D002738:Chloroquine; D011433:Propranolol; D000242:Cyclic AMP; D000527:Alprostadil; D015232:Dinoprostone; D007545:Isoproterenol; D007213:Indomethacin