Regulation by angiotensin II of phosphate transport in cardiac myocytes.
The purpose of this study was to test the hypothesis that angiotensin II (ang II) affects the transport of inorganic phosphate in adult ventricular myocytes. Ventricular myocytes were isolated from Dahl rats and allowed to take up 32P inorganic phosphate (32P-Pi). The intracellular 32P concentration increased rapidly and reached a peak at 5 min. Ang II, 10(-10) to 10(-5) M, produced a significant (P less than 0.05) and concentration-dependent reduction in 32P-Pi uptake that plateaued at 0.1 to 1.0 microM. Ang II at 1 microM produced a 30% reduction in Vmax and a slightly greater reduction in the Km of 32P-Pi uptake, compared to myocytes that were not exposed to ang II. The ang II receptor antagonist saralasin (Sar1-Val5-Ala8-angiotensin II), significantly (P less than 0.05) antagonized the action of ang II on 32P-Pi uptake. TPA (12-O-tetradecanoylphorbol-13-acetate) also produced a significant (P less than 0.05) reduction of 32P-Pi uptake, suggesting that protein kinase C is involved in the transduction of ang II effects on intracellular Pi. 32P Efflux from myocytes, pulsed with 32P-Pi and chased with Pi-free medium, was accentuated markedly by ang II; this effect was blunted by saralasin. These data suggest that ang II is capable of regulating total intracellular Pi in the heart via two actions: (i) by inhibiting uptake of Pi into the myocyte, and (ii) by increasing the efflux of phosphates out of the cell.
Sunga
P S
PS
Cardiovascular Research Laboratories, University Hospital Research Centre, University of British Columbia, Vancouver, Canada.
Rabkin
S W
SW
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D051381:Rats; D012504:Saralasin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D010710:Phosphates; D010761:Phosphorus Radioisotopes; D000804:Angiotensin II; D012504:Saralasin; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate