Alpha 1-adrenoceptor and purinoceptor agonists modulate Na-H antiport in single cardiac cells.
We investigated the effects of an alpha 1-adrenoceptor (phenylephrine) and a purinoceptor agonist (ATP), both of which accelerate the phosphoinositide turnover, on the Na-H antiport activity of rat single cardiac cells using the pH-sensitive fluorescent indicator seminaphthorhodafluor-1 (SNARF-1). Both phenylephrine, in the presence of a beta-adrenoceptor blocker, and ATP enhanced the ability of the cell to regulate its intracellular pH (pHi) after an imposed acid load. This effect was observed in HCO3-free N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) and prevented by Na-H antiport inhibitors ethylisopropylamiloride (EIPA) or amiloride. Similar results were obtained when cells were bathed in an acidic extracellular medium. Hence, the alpha 1-adrenoceptor and purinoceptor agonists activate the Na-H antiport even when it is partially inhibited by extracellular protons. To further evaluate the effects of the two neurohormones, the rate of proton efflux was estimated as a function of the magnitude of the imposed acid load. The results indicate that the agonist-induced modulation of the Na-H antiport is caused by an acceleration of its exchange activity and by a shift of its dependence on pHi toward more alkaline pH values. The agonist-mediated stimulation of the antiport was also observed in partially depolarized cells and was not dependent on intracellular Ca. Phorbol 12-myristate 13-acetate was not able to reproduce the effects of the agonists on the Na-H antiport. Conversely, the inhibitors of protein kinase C did not prevent the activation of the antiport by the neurohormones. Thus our data suggest that neither a Ca-calmodulin-dependent kinase nor protein kinase C is responsible for the alpha 1-adrenoceptor- and purinoceptor-mediated stimulation of the antiport.
Pucéat
M
M
Laboratoire de Physiologie Cellulaire Cardiaque, Institut National de la Santé et de la Recherche Médicale, Unité 241, Université Paris-Sud, Orsay, France.
Clément-Chomienne
O
O
Terzic
A
A
Vassort
G
G
D000138:Acidosis / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002469:Cell Separation; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011983:Receptors, Purinergic / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers
D000316:Adrenergic alpha-Agonists; D002352:Carrier Proteins; D011983:Receptors, Purinergic; D017923:Sodium-Hydrogen Exchangers; D000643:Ammonium Chloride; D010656:Phenylephrine; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D002118:Calcium