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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 14, 2005; DOI: 10.1124/jpet.105.092940


0022-3565/06/3162-628-635$20.00
JPET 316:628-635, 2006
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CARDIOVASCULAR

Effects of Phytoestrogens on Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase 2a and Ca2+ Uptake into Cardiac Sarcoplasmic Reticulum

Marnie L. Olson, Margaret E. Kargacin, Thomas W. Honeyman, Christopher A. Ward, and Gary J. Kargacin

Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada (M.L.O., M.E.K., G.J.K.); Department of Physiology, University of Massachusetts Medical School, Worcester, Massachusetts (T.W.H.); and Department of Physiology, Queens University, Kingston, Ontario, Canada (C.A.W.)

Phytoestrogens are naturally occurring estrogenic compounds found in plants and plant products. These compounds are also known to exert cellular effects independent of their interactions with estrogen receptors. We studied the effects of the phytoestrogens phloretin, phloridzin, genistein, and biochanin A on Ca2+ uptake into the cardiac muscle sarcoplasmic reticulum (SR). Genistein and biochanin A did not affect SR Ca2+ uptake. On the other hand, phloretin and phloridzin decreased the maximum velocity of SR Ca2+ uptake but did not affect the Hill coefficient or the Ca2+ sensitivity of uptake. Measurements of the ATPase activity of the cardiac SR Ca2+ pump (SERCA2a) revealed direct inhibitory effects of phloretin and phloridzin on SERCA2a. Neither compound induced a detectable change in the permeability of the SR membrane to Ca2+. These results indicate that phloretin and phloridzin inhibit cardiac SR Ca2+ uptake by directly inhibiting SERCA2a.


Received July 19, 2005; accepted October 13, 2005.

Address correspondence to: Dr. Gary Kargacin, Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr. N.W., Calgary, AB T2N 4N1, Canada. E-mail: kargacin{at}ucalgary.ca




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M. L. Olson, M. E. Kargacin, C. A. Ward, and G. J. Kargacin
Effects of Phloretin and Phloridzin on Ca2+ Handling, the Action Potential, and Ion Currents in Rat Ventricular Myocytes
J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 921 - 929.
[Abstract] [Full Text] [PDF]




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