| Autor: |
Jaimovich, Enrique, Mattei, César, Liberona, José Luis, Cardenas, Cesar, Estrada, Manuel, Barbier, Julien, Debitus, Cécile, Laurent, Dominique, Molgó, Jordi |
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| Zdroj: |
FEBS Letters; Apr2005, Vol. 579 Issue 10, p2051-2057, 7p |
| Abstrakt: |
Abstract: Xestospongin B, a macrocyclic bis-1-oxaquinolizidine alkaloid extracted from the marine sponge Xestospongia exigua, was highly purified and tested for its ability to block inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release. In a concentration-dependent manner xestospongin B displaced [3H]IP3 from both rat cerebellar membranes and rat skeletal myotube homogenates with an EC50 of 44.6±1.1μM and 27.4±1.1μM, respectively. Xestospongin B, depending on the dose, suppressed bradykinin-induced Ca2+ signals in neuroblastoma (NG108-15) cells, and also selectively blocked the slow intracellular Ca2+ signal induced by membrane depolarization with high external K+ (47mM) in rat skeletal myotubes. This slow Ca2+ signal is unrelated to muscle contraction, and involves IP3 receptors. In highly purified isolated nuclei from rat skeletal myotubes, Xestospongin B reduced, or suppressed IP3-induced Ca2+ oscillations with an EC50 =18.9±1.35μM. In rat myotubes exposed to a Ca2+-free medium, Xestospongin B neither depleted sarcoplasmic reticulum Ca2+ stores, nor modified thapsigargin action and did not affect capacitative Ca2+ entry after thapsigargin-induced depletion of Ca2+ stores. Ca2+-ATPase activity measured in skeletal myotube homogenates remained unaffected by Xestospongin B. It is concluded that xestospongin B is an effective cell-permeant, competitive inhibitor of IP3 receptors in cultured rat myotubes, isolated myonuclei, and neuroblastoma (NG108-15) cells. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
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