Prostaglandins alter intracellular levels of cAMP in palate mesenchyme cells, and cAMP influences strongly the synthesis of extracellular matrix macromolecules of those cells. Such findings suggest that regulation of prostaglandin synthesis may be a developmentally significant event in the formation of the secondary palate. Therefore, these studies aim to explore the extent to which growth and differentiation of the palate is regulated by enzyme activities responsible for availability of precursors (i.e. arachidonic acid) to prostaglandins. The ontogeny of phospholipase A activity during normal and abnormal growth and differentiation of the palate will be determined by use of thin layer and gas liquid chromatography. Relations between phospholipase A activities and growth and differentiation of palate will be assessed with primary cultures of mouse embryo palate mesenchyme cells. The degree to which various agents alter phospholipase A activities, synthesis of DNA and synthesis of glycosaminoglycans will be determined by thin layer chromatography, gas liquid chromatography, and scintillation spectrometry. These techniques, along with radioimmunoassay, will be used to determine relations between catecholamine-induced elevation of cAMP, or glucocorticoid inhibition, and EGF-stimulation, of proliferation in palate mesenchyme cells and phospholipase A activities. The ability of arachidonic acid or its metabolites to reverse the effects of various inhibitors of phospholipase A on palate cell growth and differentiation will be taken as evidence for specificity of the inhibitors and indicate which processes are regulated by a specific metabolite (prostaglandin). The objectives of the proposed research are: (1) to define relations between mobilization and metabolism of arachidonic acid to proliferation and function of embryonic palate cells, (2) to explore a basis for metabolic control over palate cell growth and function by potentially developmentally relevant effectors of palate formation, and (3) to determine whether the tenable hypothesis that phospholipase A2 activity may serve as a metabolic site for glucocorticoid-modulation of palate formation, in vivo, is valid.
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