Stimulation of the Na+/Ca2+ exchanger by phenylephrine, angiotensin II and endothelin 1

Cherry Ballard, Stephen Schaffer

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88 Scopus citations


The Na+/Ca2+ exchanger plays an important role in the maintenance of calcium homeostasis in the heart. Therefore, factors which regulate the exchanger have a significant impact on cardiac function. Previously, we showed that the non-hydrolysable GTP analog, 5′guanylyl imidodiphosphate [Gpp(NH)p], stimulates Na+/Ca2+ exchange activity, implying the involvement of a G protein in exchanger regulation. In this study, we examined the effect of G protein agonists on Na+/Ca2+ exchanger activity. Isoproterenol, a Gs agonist, had no effect on exchanger activity. Likewise, the Gi agonist, carbachol, did not influence Na+/Ca2+ exchanger activity. Since these G proteins couple to the adenylate cyclase system, it would appear that cAMP-linked events do not regulate the Na+/Ca2+ exchanger. We next examined the influence of Gq-linked agonists on exchanger activity. Phenylephrine, an α1-adrenergic agonist, increased Na+/Ca2+ exchanger activity up to 111% with an EC50 of 21 μM. Moreover, the Na+/Ca2+ exchanger activity was enhanced by angiotensin II and endothelin 1, which caused maximal stimulation of exchanger activity up to 125% and 211%, respectively. The selective protein kinase C inhibitor chelerythrine significantly attenuated the ability of phenylephrine and angiotensin II to stimulate the Na+/Ca2+ exchanger. In addition, the protein kinase C activator, phorbol 12-myristate 13-acetate, stimulated exchanger activity by 32%, raising the possibility that all three Gq agonists mediate their actions in part through the promotion of phospholipase C activity and the subsequent activation of protein kinase C. The contribution of Na+/Ca2+ exchange to the actions of phenylephrine, angiotensin II, and endothelin 1 is discussed.

Original languageEnglish
Pages (from-to)11-17
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Issue number1
StatePublished - Jan 8 1996


  • Angiotensin II
  • Endothelin 1
  • G proteins
  • Na/Ca exchange
  • Phenylephrine
  • Protein kinase C

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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