Functional role of Na+/H+ exchanger in Ca2+ influx mediated via human endothelin type A receptor stably expressed in Chinese hamster ovary cells.

This study examines the functional role of Na+/H+ exchanger (NHE) in Ca2+ influx mediated by human endothelin type A receptor (ET(A)R) expressed in Chinese hamster ovary (CHO) cells. Endothelin-1 (ET-1) increased extracellular acidification rate (ECAR), which was abolished by 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an NHE inhibitor. EIPA and KB-R7943, a Na+/Ca2+ exchanger (NCX) inhibitor, inhibited ET-1-induced sustained increases in intracellular Ca2+ concentration ([Ca2+]i), and EIPA had no effect on [Ca2+]i after KB-R7943 treatment. ET-1-elicited sustained [Ca2+]i increase was suppressed by reducing extracellular Na+ concentration. These results suggest that possible coupling of NHE with NCX via Na+ transport is involved in ET(A)R-mediated sustained [Ca2+]i increase.

[1]  T. Nishiya,et al.  Endothelin-1 decreases [Ca2+]i via Na+/Ca2+ exchanger in CHO cells stably expressing endothelin ETA receptor. , 2007, European journal of pharmacology.

[2]  G. Heusch,et al.  Regulation and role of the presynaptic and myocardial Na+/H+ exchanger NHE1: effects on the sympathetic nervous system in heart failure. , 2007, Cardiovascular drug reviews.

[3]  H. Cingolani,et al.  Sodium-hydrogen exchanger, cardiac overload, and myocardial hypertrophy. , 2007, Circulation.

[4]  T. Nishiya,et al.  Characterization of noradrenaline-induced increases in intracellular Ca2+ levels in Chinese hamster ovary cells stably expressing human alpha1A-adrenoceptor. , 2007, Journal of pharmacological sciences.

[5]  L. Fliegel,et al.  Physiological role and regulation of the Na+/H+ exchanger. , 2006, Canadian journal of physiology and pharmacology.

[6]  Misuk Kang,et al.  Endothelin-1 and PKC Induce Positive Inotropy Without Affecting pHi in Ventricular Myocytes , 2006, Experimental biology and medicine.

[7]  D. Bers,et al.  Cardiac myocytes Ca2+ and Na+ regulation in normal and failing hearts. , 2006, Journal of pharmacological sciences.

[8]  Y. Okamoto,et al.  Ca2+ entry channels involved in endothelin-1-induced contractions of vascular smooth muscle cells. , 2005, Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi.

[9]  A. Christopoulos,et al.  Evidence for Pleiotropic Signaling at the Mouse β3-Adrenoceptor Revealed by SR59230A [3-(2-Ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol Oxalate] , 2005, Journal of Pharmacology and Experimental Therapeutics.

[10]  K. Venkatachalam,et al.  Calcium entry mediated by SOCs and TRP channels: variations and enigma. , 2004, Biochimica et biophysica acta.

[11]  T. Masaki,et al.  Molecular mechanisms for the activation of voltage-independent Ca2+ channels by endothelin-1 in chinese hamster ovary cells stably expressing human endothelin(A) receptors. , 2002, Molecular pharmacology.

[12]  D. Barber,et al.  The changing face of the Na+/H+ exchanger, NHE1: structure, regulation, and cellular actions. , 2002, Annual review of pharmacology and toxicology.

[13]  T. Taniguchi,et al.  Rapid acid extrusion response triggered by α1 adrenoceptor in CHO cells , 2001 .

[14]  P. Molenaar,et al.  The human heart endothelin system: ET-1 synthesis, storage, release and effect. , 2000, Trends in pharmacological sciences.

[15]  J. W. Parce,et al.  The cytosensor microphysiometer: biological applications of silicon technology. , 1992, Science.