Angiotensin II Rapidly Increases Phosphatidate-Phosphoinositide Synthesis and Phosphoinositide Hydrolysis and Mobilizes Intracellular Calcium in Cultured Arterial Muscle Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 1984-12, Vol.81 (24), p.7812-7816
• Main Authors: Smith, Jeffrey Bingham, Smith, Lucinda, Brown, E. Renee, Barnes, Dee, Sabir, Mohammad A., Davis, John S., Farese, Robert V.
• Format: Article
• Language: English
• Subjects: angiotensin II; Angiotensin II - pharmacology; Animals; Aorta; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; arteries; Calcium; Calcium - metabolism; Cell culture techniques; Cell membranes; Cells, Cultured; Cultured cells; Hydrolysis; Inositols; Kinetics; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Phosphatidic Acids - biosynthesis; Phosphatidylinositols; Phosphatidylinositols - biosynthesis; Phosphatidylinositols - metabolism; Phospholipids; Rats; Rats, Inbred Strains; Smooth muscle
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.81.24.7812

Smooth muscle cells were cultured from rat thoracic aorta and labeled to a stable specific activity with45Ca2+, myo-[2-3H]inositol, or32Pi. The efflux of45Ca2+was monitored over 10-sec intervals. Angiotensin II (AII) increased the amount of45Ca2+lost by 5-fold in the first 10-sec interval after the addition of AII and by 10-fold in the second 10-sec interval. AII-stimulated45Ca2+release was blocked by the angiotensin antagonist [1-sarcosine, 8-leucine]AII and by La3+. The removal of external Ca2+had no effect on AII-stimulated45Ca2+release. Depolarization with high external K+only slightly increased45Ca2+efflux and had no effect on AII-induced45Ca2+release. AII had no effect on the initial rate of45Ca2+influx. These results indicate that the rapid45Ca2+efflux evoked by AII is probably due to the release of45Ca2+sequestered intracellularly rather than to an increase in the Ca2+permeability of the plasma membrane. AII provoked rapid increases in the levels of phosphatidic acid and phosphoinositides in the cells. These increases in phospholipids were associated with increases in phospholipase C-generated inositol phosphates (tri-, di-, and mono-). It appears that AII simultaneously increases phosphoinositide hydrolysis and synthesis in vascular smooth muscle, and both phospholipid effects may contribute to inositol triphosphate generation, which was sufficiently rapid to have a role in intracellular Ca2+mobilization.