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.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
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Oral Biology and Medicine Study Section (OBM)
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Thomas Jefferson University
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Hamre, K M; Chepenik, K P; Goldowitz, D (1995) The annexins: specific markers of midline structures and sensory neurons in the developing murine central nervous system. J Comp Neurol 352:421-35
Chepenik, K P; Shipman-Appasamy, P; Ahn, N et al. (1995) Developmental regulation of various annexins in the embryonic palate of the mouse: dexamethasone affects expression of annexin-1. J Craniofac Genet Dev Biol 15:171-81
Chepenik, K P; Diaz, A; Jimenez, S A (1994) Epidermal growth factor coordinately regulates the expression of prostaglandin G/H synthase and cytosolic phospholipase A2 genes in embryonic mouse cells. J Biol Chem 269:21786-92
Chepenik, K P; Wykle, R L (1992) Synthesis of platelet activating factor and metabolism of related lipids in embryonic cells. Biochim Biophys Acta 1126:192-8
London, F S; Caamano-Haigh, R; Chepenik, K P (1989) Dexamethasone does not interfere with hormone-sensitive PI hydrolysis. Teratology 39:121-6
Chepenik, K P; Haystead, T A (1989) Epidermal growth factor alters metabolism of inositol lipids and activity of protein kinase C in mouse embryo palate mesenchyme cells. J Craniofac Genet Dev Biol 9:285-301
Chepenik, K P (1989) Epidermal growth factor modulates release of arachidonic acid from embryonic cells. Lipids 24:829-32
Chepenik, K P; Grunwald, G B (1988) Effects of epidermal growth factor and phorbol 12-myristate 13-acetate on protein phosphorylation in mouse embryo palate mesenchyme cells in vitro. J Craniofac Genet Dev Biol 8:147-53
Shipman, P M; Schmidt, R R; Chepenik, K P (1988) Relation between arachidonic acid metabolism and development of thymocytes in fetal thymic organ cultures. J Immunol 140:2714-20
Chabot, M C; Chepenik, K P (1987) Cyclic adenosine-3',5'-monophosphate alters hydrolysis of phospholipids by mouse embryo palate mesenchyme cells. J Craniofac Genet Dev Biol 7:53-8

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