Modulation of phosphoinositide metabolism in aortic smooth muscle cells by allylamine

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · Experimental and Molecular Pathology; (USA)

DOI:https://doi.org/10.1016/0014-4800(90)90023-7· OSTI ID:6217333

Cox, L R; Murphy, S K; Ramos, K ^[1]

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1. Philadelphia College of Pharmacy and Science, PA (USA)

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.

• OSTI ID: 6217333
• Journal Information: Experimental and Molecular Pathology; (USA), Vol. 53:1; ISSN 0014-4800
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 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
550501* - Metabolism- Tracer Techniques
560300 - Chemicals Metabolism & Toxicology