Interactions of 6-gingerol and ellagic acid with the cardiac sarcoplasmic reticulum Ca2+-ATPase

Alexander Y. Antipenko, Andrew I. Spielman, Madeleine A. Kirchberger

Research output: Contribution to journalArticle

Abstract

The inotropic/lusitropic effects of β-adrenergic agonists on the heart are mediated largely by protein kinase A (PKA)-catalyzed phosphorylation of phospholamban, the natural protein regulator of the Ca2+ pump present in sarcoplasmic reticulum (SR) membranes. Gingerol, a plant derivative, is known to produce similar effects when tested in isolated cardiac muscle. The purpose of the present study was to compare the effects of gingerol and another plant derivative, ellagic acid, on the kinetics of the SR Ca2+ pump with those of PKA-catalyzed phospholamban phosphorylation to elucidate their mechanisms of Ca2+ pump regulation. As previously demonstrated for PKA, 50 μM gingerol or ellagic acid increased V(max(Ca)) of Ca2+ uptake and Ca2+-ATPase activity assayed at millimolar ATP concentrations in light cardiac SR vesicles. Unlike PKA, which decreases K(m(Ca)), neither compound had a significant effect on K(m(Ca)) in unphosphorylated vesicles. However, gingerol increased K(m(Ca)) in phosphorylated vesicles, in which Ca2+ uptake was significantly increased further at saturating Ca2+ and remained unchanged at subsaturating Ca2+. An inhibition of Ca2+ uptake by gingerol at micromolar MgATP concentrations was overcome with increasing MgATP concentrations. The stimulation of Ca2+ uptake attributable to gingerol in unphosphorylated microsomes at saturating Ca2+ was 30% to 40% when assayed at 0.05 to 2 mM MgATP and only about 12% in phosphorylated microsomes as well as in rabbit fast skeletal muscle light SR. The present results support the view that an ATP-dependent increase in V(max(Ca)) of the SR Ca2+ pump plays an important role in mediating cardiac contractile responses to gingerol and phospholamban-dependent β-adrenergic stimulation.

Original languageEnglish (US)
Pages (from-to)227-234
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume290
Issue number1
StatePublished - Jul 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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