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Author Cox, L. R. ♦ Murphy, S. K. ♦ Ramos, K.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword BASIC BIOLOGICAL SCIENCES ♦ RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT. ♦ AMINES ♦ BIOCHEMICAL REACTION KINETICS ♦ ANIMAL CELLS ♦ CELL PROLIFERATION ♦ PHOSPHOLIPIDS ♦ METABOLISM ♦ AORTA ♦ ENZYME ACTIVITY ♦ ENZYME INHIBITORS ♦ MUSCLES ♦ PHENOTYPE ♦ PHORBOL ESTERS ♦ PHOSPHORUS 32 ♦ PHOSPHOTRANSFERASES ♦ RATS ♦ TRACER TECHNIQUES ♦ TRITIUM COMPOUNDS ♦ ANIMALS ♦ ARTERIES ♦ BETA DECAY RADIOISOTOPES ♦ BETA-MINUS DECAY RADIOISOTOPES ♦ BLOOD VESSELS ♦ BODY ♦ CARCINOGENS ♦ CARDIOVASCULAR SYSTEM ♦ DAYS LIVING RADIOISOTOPES ♦ ENZYMES ♦ ESTERS ♦ HYDROGEN COMPOUNDS ♦ ISOTOPE APPLICATIONS ♦ ISOTOPES ♦ KINETICS ♦ LIGHT NUCLEI ♦ LIPIDS ♦ MAMMALS ♦ NUCLEI ♦ ODD-ODD NUCLEI ♦ ORGANIC COMPOUNDS ♦ ORGANIC PHOSPHORUS COMPOUNDS ♦ ORGANS ♦ PHOSPHORUS ISOTOPES ♦ PHOSPHORUS-GROUP TRANSFERASES ♦ RADIOISOTOPES ♦ REACTION KINETICS ♦ RODENTS ♦ TRANSFERASES ♦ VERTEBRATES ♦ Metabolism- Tracer Techniques ♦ Chemicals Metabolism & Toxicology
Abstract Aortic smooth muscle cells (SMC) modulate from a contractile to a proliferative phenotype upon subchronic exposure to allylamine. The present studies were designed to determine if this phenotypic modulation is associated with alterations in the metabolism of membrane phosphoinositides. 32P incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), and phosphatidic acid (PA) was lower by 31, 35, and 22%, respectively, in SMC from allylamine-treated animals relative to controls. In contrast, incorporation of (3H)myoinositol into inositol phosphates did not differ in allylamine cells relative to control cells. Exposure to dibutyryl (db) cAMP (0.2 mM) and theophylline (0.1 mM) reduced 32P incorporation into PIP and PIP2 in SMC from both experimental groups. Under these conditions, a decrease in (3H)myoinositol incorporation into inositol 1-phosphate was only observed in allylamine cells. The effects of db cAMP and theophylline in allylamine and control SMC correlated with a marked decrease in cellular proliferation. These results suggest that alterations in phosphoinositide synthesis and/or degradation contribute to the enhanced proliferation of SMC induced by allylamine. To further examine this concept, the effects of agents which modulate protein kinase C (PKC) activity were evaluated. Sphingosine (125-500 ng/ml), a PKC inhibitor, decreased SMC proliferation in allylamine, but not control cells. 12-O-Tetradecanoylphorbol-13-acetate (1-100 ng/ml), a PKC agonist, stimulated proliferation in control cells, but inhibited proliferation in cells from allylamine-treated animals. We conclude that allylamine-induced phenotypic modulation of SMC is associated with alterations in phosphoinositide metabolism.
ISSN 00144800
Educational Use Research
Learning Resource Type Article
Publisher Date 1990-08-01
Publisher Place United States
Journal Experimental and Molecular Pathology
Volume Number 53
Issue Number 1


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