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Higenamine이 심근 Sarcoplasmic Reticulum의 칼슘운반에 미치는 영향에 관한 연구

The Effect of Higenamine on the Calcium Transport of Cardiac Sarcoplasmic Reticulum

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Higenamine(dl-demethylcoclaurine, dl-1-(4-hydroxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrah-ydroisoquinoline hydrochloride), which has recently been isolated from Aconite root by Drs. Kosuge and Yokota, has known to be the main cardiotonic component of the Aconite root. The present study was undertaken to investigate the effects of Higenamine on the calcium binding and release and ATPase activity of fragmented cardiac sarcoplasmic reticulum under in vitro condition. The calcium binding and release of sarcoplasmic reticulum were measured by using the double-beam spectrophotometer and the calcium sensitive dye, murexide. In the presence of 10<sup>-4</sup> ~ 5 X 10<sup>-3</sup>M of Higenamine, the maximal calcium binding and the initial binding rate of porcine cardiac sarcoplasmic reticulum were inhibited dose dependently by up to 43%. However, the calcium release from cardiac sarcoplasmic reticulum, which was loaded with Ca<sup>++</sup>(50μM), was stimulated in dose dependent manner. When incubated in the medium of 20 mM Tris-maleate(pH 7.0), 100 mM KCl, 10 mM MgCl<sub>2</sub>, 0.05mM CaCl<sub>2</sub> and 0.014 ~ 1 mM Tris-ATP at 30˚C in the presence of Higenamine (10<sup>-4</sup> ~ 5 X 10<sup>-3</sup>M), both Ca<sup>++</sup>-and Mg<sup>++</sup>-ATPase of sarcoplasmic reticulum were inhibited non-competitively by Higenamine and values of K<sub>i</sub> were 4.896 mM and 6.875 mM respectively. It is suggested from the above findings that the cardiotonic effects of Higenamine might be partially explained by the inhibition of calcium binding and the stimulation of calcium release from the sarcoplasimic reticulum which may increase the free intracellular calcium that is available in the contraction of the cardiac muscle fiber.

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