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Sustained diacylglycerol formation from inositol phospholipids in angiotensin II-stimulated vascular smooth muscle cells

Journal Article · · J. Biol. Chem.; (United States)
OSTI ID:5690945
; ; ; ; ;

Angiotensin II acts on cultured rat aortic vascular smooth muscle cells to stimulate phospholipase C-mediated hydrolysis of membrane phosphoinositides and subsequent formation of diacylglycerol and inositol phosphates. In intact cells, angiotensin II induces a dose-dependent increase in diglyceride which is detectable after 5 s and sustained for at least 20 min. Angiotensin II (100 nM)-stimulated diglyceride formation is biphasic, peaking at 15 s (227 +/- 19% control) and at 5 min (303 +/- 23% control). Simultaneous analysis of labeled inositol phospholipids shows that at 15 s phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 4-phosphate (PIP) decline to 52 +/- 6% control and 63 +/- 5% control, respectively, while phosphatidylinositol (PI) remains unchanged. In contrast, at 5 min, PIP2 and PIP have returned toward control levels (92 +/- 2 and 82 +/- 4% control, respectively), while PI has decreased substantially (81 +/- 2% control). The calcium ionophore ionomycin (15 microM) stimulates diglyceride accumulation but does not cause PI hydrolysis. 4 beta-Phorbol 12-myristate 13-acetate, an activator of protein kinase C, inhibits early PIP and PIP2 breakdown and diglyceride formation, without inhibiting late-phase diglyceride accumulation. Thus, angiotensin II induces rapid transient breakdown of PIP and PIP2 and delayed hydrolysis of PI. The rapid attenuation of polyphosphoinositide breakdown is likely caused by a protein kinase C-mediated inhibition of PIP and PIP2 hydrolysis. While in vascular smooth muscle stimulated with angiotensin II inositol 1,4,5-trisphosphate formation is transient, diglyceride production is biphasic, suggesting that initial and sustained diglyceride formation from the phosphoinositides results from different biochemical and/or cellular processes.

Research Organization:
Harvard Medical School, Boston, MA
OSTI ID:
5690945
Journal Information:
J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 13; ISSN JBCHA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
ANGIOTENSIN
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
CARBOHYDRATES
CARBOXYLESTERASES
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CHEMICAL REACTIONS
DECOMPOSITION
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYMES
ESTERASES
ESTERS
GLOBULINS
GLYCEROL
HYDROLASES
HYDROLYSIS
HYDROXY COMPOUNDS
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPASE
LIPIDS
LYSIS
MAMMALS
MEMBRANES
MONOSACCHARIDES
MUSCLES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHATES
PHOSPHOLIPIDS
PHOSPHORUS COMPOUNDS
PROTEINS
RATS
REACTION KINETICS
RODENTS
SACCHARIDES
SOLVOLYSIS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASOCONSTRICTORS
VERTEBRATES