Protein kinase C mechanism enhances vascular muscle relaxation by the Ca2+ antagonist, Ro 40-5967

Journal of Vascular Research
K Hermsmeyer, K Miyagawa

Abstract

Actions of the novel Ca2+ antagonist, Ro 40-5967, which displays unusual efficacy against endothelin (ET)-induced contractions, were studied in isolated vascular muscle cells (VMCs) using the fluorescent protein kinase C (PKC) indicator, BODIPY 12 alpha-phorbol ester 13 beta-acetate (PBA-BODIPY). High-sensitivity (photon-counting) digital-imaging microscopy quantified PKC distribution within VMCs and showed translocation from the cytosol to the cell surface membrane on stimulation with ET. ET (1 nM) stimulated translocation of PBA-BODIPY fluorescence that peaked at 4 min, increasing from 19 +/- 2% to 29 +/- 2% surface membrane (edge) distribution (n=44, p<0.05). Increases in membrane-associated PKC due to translocation began within 2 min and persisted for about 10 min, after which a gradual decline to control levels occurred. Upon exposure to Ro 40-5967 (10 microM), there was an inhibition of fluorescence intensity throughout the cell. Average fluorescence intensity decreased to 84 +/- 4% (n=20, p<0.05) of that in prestimulus controls. Cell/membrane was also reduced to below unstimulated control levels. Amlodipine failed to decrease PKC fluorescence intensity or translocation to the surface membrane. These data suggest that the...Continue Reading

Citations

Oct 17, 1998·British Journal of Pharmacology·D SarseroJ A Angus
Nov 18, 2000·British Journal of Pharmacology·S J PotocnikM A Hill
Nov 19, 2005·Journal of Pharmacological Sciences·Koichi HayashiTakao Saruta
Feb 20, 2007·Circulation Research·Koichi HayashiTakao Saruta
Feb 19, 1998·The Journal of Clinical Endocrinology and Metabolism·R D MinshallK Hermsmeyer
May 22, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Xavier F FigueroaBrian R Duling

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