Alpha 1-adrenergic stimulation of Na-H exchange in cardiac myocytes.
The activation of Na-H exchange in adult rat heart myocytes was characterized in response to a phorbol ester (phorbol 12-myristate 13-acetate) and an alpha 1-adrenergic agonist [6-fluoronorepinephrine (6F-NE)]. Transport activation was assessed by determining the initial rate with which intracellular pH (pHi) was returned from an acid pulse and by following changes in steady-state pHi; pHi was determined by a pH-sensitive fluorescent dye. Both agonists shifted the intracellular pH dependence of Na-H exchange by 0.10-0.15 pH units in the alkaline direction. This shift was prevented by the presence of sphingosine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), inhibitors of protein kinase C. The agonists also alkalinized pHi at steady state. The alkalinization by 6F-NE was blocked by prazosin and H-7. This indicates that the adrenergic stimulation of cardiac Na-H exchange is mediated by an alpha 1-adrenergic mechanism and very likely involves the activation of protein kinase C.
Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322.
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Wallert
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Fröhlich
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000031:analogs & derivatives / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017923:Sodium-Hydrogen Exchangers; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002352:Carrier Proteins; D007546:Isoquinolines; D010879:Piperazines; D017923:Sodium-Hydrogen Exchangers; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C024884:6-fluoronorepinephrine; D011493:Protein Kinase C; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine