| Summary: | 碩士 === 國立臺灣大學 === 毒理學研究所 === 83 === The purpose of this study is aimed to the effects of xanthones (xanthone and norathyriol) on the calcium homeostasis from skeletal and smooth muscles.
Our results showed that both xanthone and norathyriol
increased muscle contraction on the mouse phrenic diaphragm and
induced calcium release from sarcoplasmic reticulum vesicles.
xanthone and norathyriol were also shown to increase
[3H]ryanodine binding. At the same time, we used [3H]ryanodine
binding to study the relationship of Mg2+, caffeine, norathyriol
and xanthone on the ryanodine receptor. These observations show
that xanthone and norathyriol induced calcium release is due to
a direct interaction with the calcium release channel from
sarcoplasmic reticulum and are different binding sites. On the
other hand, norathyriol inhibited the sarcoplasmic reticulum
calcium ATPase activity but xanthone activated the calcium
ATPase activity. We suggest xanthone has another effect because
its difficulty to penetrate the cell membrane. This reason to
explain the different manner between muscle contraction and
calcium release caused by these two compounds.
Xanthone inhibited NE and PE induced phasic and tonic
contractions in the thoracic aorta of the rat, and no effects on
caffeine-induced phasic contraction or phosphoinositide
breakdown. Xanthone also inhibits 45Ca2+ influx and the muscle
contraction caused by high potassium. When we used EIA kit to
detect the content of cAMP, we found xanthone dose-dependently
increased cAMP content. cAMP relaxed the rat aorta ring by way
of hyperpolarizing the cell membrane and then inhibiting
depolarization and voltage-operated calcium channels and also
activating calcium pump to decrease cytosolic Ca2+
concentration, inhibited myosin light chain kinase
phosphorylation. We found xanthone like calcium channel blocker
and the vasorelaxation effect of xanthone was independent on
endothelium of smooth muscle cells.
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