Open AccessMechanism of Action of Sarcoplasmic Reticulum Calcium‐Uptake Activators
Author(s) -
BerrebiBertrand Isabelle,
Lahouratate Philippe,
Lahouratate Véronique,
Camelin Jean Claude,
Guibert Jacqueline,
Bril Antoine
Publication year - 1997
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1997.t01-1-00801.x
Subject(s) - phospholamban , ellagic acid , endoplasmic reticulum , calcium , chemistry , microsome , atpase , biochemistry , cardiac muscle , ouabain , endocrinology , biology , enzyme , antioxidant , sodium , polyphenol , organic chemistry
The Ca 2+ uptake by the sarcoplasmic reticulum (SR) can be affected by direct modulation of the Ca 2+ pump or by removing the inhibitory effect of dephosphorylated phospholamban. The effect of these mechanisms was assessed using ellagic acid and 1‐(3,4‐dimethoxyphenyl)‐3‐dodecanone. Both compounds (30 μmol/l) enhanced SR‐Ca 2+ uptake in rabbit cardiomyocytes by 65.3±413% and 44.3±56.7% for 1‐(3,4‐dimethoxyphenyl)‐3‐dodecanone and ellagic acid, respectively (at pCa 6.2). A similar effect was observed in cardiac SR microsomes (59.5±7.4% and 45.1±6.7) with 30 μmol/l 1‐(3,4‐dimethodoxyphenyl)‐3‐dodecanone and ellagic acid, respectively. 1‐(3,4‐DimethoxyphenyI)‐3‐dodecanone increased Ca 2+ storage by cardiac SR microsomes mainly at high [Ca 2+ ] with a 57% increase of V max , whereas ellagic acid increased V max to a smaller extent (22%) and stimulated Ca 2+ uptake at lower [Ca 2+ ] with a leftward‐shift of the pCa/ATPase relationship by pCa 0.24. Ellagic acid also differed from 1‐(3,4‐dimethoxylphenyl)‐3‐dodecanone in that it produced a Ca 2+ sensitizing effect only in cardiac SR microsomes (by pCa 0.3) whereas 1‐(3,4‐dimethoxyphenyl)‐3‐dodecanone stimulated the ATPase, at saturating Ca 2+ , in both cardiac and skeletal muscle SR vesicles. It is suggested that 1‐(3.4‐dimethoxypheny1)‐3‐dodecanone stimulates directly the Ca 2+ ‐ATPase activity, in contrast to ellagic acid which enhances the cardiac SR‐Ca 2+ uptake by interacting with phospholamban, as confirmed by the lack of additive effect between ellagic acid and monoclonal antibodies raised against phospholamban. 1‐(3,4‐dimethoxyphenyl)‐3‐dodecanone and ellagic acid constitute attractive pharmacological tools to investigate the functional consequences of enhancing SR Ca 2+ , uptake by affecting different mechanisms.