Phorbol ester activation of the rat vascular myocyte Na(+)-H(+) exchanger isoform 1

Hypertension
M Siczkowski, L L Ng

Abstract

Vascular myocytes from the spontaneously hypertensive rat (SHR) demonstrate elevated Na(+)-H(+) exchanger activity associated with increased cell proliferation and hyperresponsiveness to agonists such as phorbol esters. Since the Na(+)-H(+) exchanger isoform 1 (NHE-1) is stimulated by protein kinase C, we have investigated the effects of phorbol esters on NHE-1 activity and its phosphorylation in vascular myocytes of these rats. SHR cells demonstrated a larger alkalinization response to 12-O-tetradecanoylphorbol 13-acetate than Wistar-Kyoto rat (WKY) cells. Kinetic analyses indicated that whereas 12-O-tetradecanoylphorbol 13-acetate increased the maximal transport capacity of NHE-1 in both cell types, affinity for H+ was increased in WKY cells and cooperativity for H+ at the internal modifier site was reduced in SHR cells. In neither cell type was the subcellular distribution of NHE-1 altered by phorbol ester stimulation. NHE-1 phosphorylation was markedly reduced in WKY cells stimulated by the phorbol ester, an effect abolished by inhibition of protein kinase C. In contrast, NHE-1 phosphorylation in quiescent SHR cells was approximately double that of WKY cells and was reduced after phorbol ester treatment. Inhibition of prote...Continue Reading

References

Dec 18, 1989·FEBS Letters·P D DavisS E Wilkinson
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Citations

Feb 26, 2003·European Journal of Pharmacology·Ichiro WakabayashiYoko Sotoda
Oct 22, 2008·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Feng J He, Graham A MacGregor
Feb 2, 2006·Journal of Vascular Research·Ichiro WakabayashiKlaus Groschner
Aug 22, 2012·Journal of Vascular Research·Ebbe Boedtkjer, Christian Aalkjaer
Sep 12, 2002·Expert Opinion on Therapeutic Targets·Karmazyn Morris
May 7, 2004·American Journal of Physiology. Cell Physiology·Elaine BeemMark S Segal
Mar 10, 1999·The American Journal of Physiology·S N OrlovP Hamet
Oct 12, 2019·Hipertensión y riesgo vascular·A M Yeves, I L Ennis
Mar 1, 1997·Metabolism: Clinical and Experimental·M SiczkowskiL L Ng

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