Ay. Antipenko et al., Interactions of 6-gingerol and ellagic acid with the cardiac sarcoplasmic reticulum Ca2+-ATPase, J PHARM EXP, 290(1), 1999, pp. 227-234
Citations number
29
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
The inotropic/lusitropic effects of p-adrenergic agonists on the heart are
mediated largely by protein kinase A (PKA)-catalyzed phosphorylation of pho
spholamban, the natural protein regulator of the Ca2+ pump present in sarco
plasmic reticulum (SR) membranes. Gingerol, a plant derivative, is known to
produce similar effects when tested in isolated cardiac muscle. The purpos
e of the present study was to compare the effects of gingerol and another p
lant derivative, ellagic acid, on the kinetics of the SR Ca2+ pump with tho
se of PKA-catalyzed phospholamban phosphorylation to elucidate their mechan
isms of Ca2+ pump regulation. As previously demonstrated for PKA, 50 mu M g
ingerol or ellagic acid increased V-max(Ca) of Ca2+ uptake and Ca2+-ATPase
activity assayed at millimolar ATP concentrations in light cardiac SR vesic
les. Unlike PKA, which decreases K-m(Ca), neither compound had a significan
t effect on K-m(Ca) in unphosphorylated vesicles. However, gingerol increas
ed K-m(Ca) in phosphorylated vesicles, in which Ca2+ uptake was significant
ly increased further at saturating Ca2+ and remained unchanged at subsatura
ting Ca2+. An inhibition of Ca2+ uptake by gingerol at micromolar MgATP con
centrations was overcome with increasing MgATP concentrations. The stimulat
ion 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 on
ly about 12% in phosphorylated microsomes as well as in rabbit fast skeleta
l muscle light SR. The present results support the view that an ATP-depende
nt increase in V-max(Ca) of the SR Ca2+ pump plays an important role in med
iating cardiac contractile responses to gingerol and phospholamban-dependen
t beta-adrenergic stimulation.