Cyclic AMP inhibits the release of prostaglandins and arachidonic acid from cultures of mouse embryo palate mesenchyme cells.
Mouse embryo palate mesenchyme (MEPM) cells are able to synthesize and respond to prostaglandins. However, mechanisms that regulate their synthesis in these cells are not known. Cyclic adenosine 3',5' monophosphate (cAMP) has been implicated as being involved in differentiation of the palate, accumulates in MEPM cells in response to stimulation with selected prostaglandins, and has been found to modulate synthesis of prostaglandins by other cells and tissues. Therefore, we have investigated whether cAMP modulates synthesis of prostaglandins by MEPM mesenchyme cells and partially characterized the metabolic site at which such modulation occurs. We found that treatment of MEPM cells with various agents to stimulate a seven- to 100-fold increase in intracellular levels of cAMP inhibited release of various prostaglandins by at least 50%. Similarly, elevation of intracellular levels of cAMP inhibited release of radiolabeled arachidonic acid from membrane phospholipids by as much as 27%. The inhibitory effects of cAMP on release of prostaglandins from MEPM cells could be almost completely overcome by the addition of arachidonic acid to the culture medium. We interpret these data to mean that there is a regulatory cycle in MEPM cells in which intracellular levels of cAMP regulates synthesis of prostaglandins and prostaglandins regulate accumulation of cAMP and regulation of synthesis of prostaglandins by cAMP is predominantly through inhibition of a phospholipase.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D003238:Connective Tissue / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology*; D004622:Embryo, Mammalian; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010159:Palate / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D013806:Theophylline / Q000031:analogs & derivatives*
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D003994:Bucladesine; D013806:Theophylline; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine