Xestospongin B, a competitive inhibitor of IP3-mediated Ca2+ signalling in cultured rat myotubes, isolated myonuclei, and neuroblastoma (NG108-15) cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue FEBS Letters Année : 2005

Xestospongin B, a competitive inhibitor of IP3-mediated Ca2+ signalling in cultured rat myotubes, isolated myonuclei, and neuroblastoma (NG108-15) cells

Résumé

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 (IP(3))-induced Ca(2+) release. In a concentration-dependent manner xestospongin B displaced [(3)H]IP(3) from both rat cerebellar membranes and rat skeletal myotube homogenates with an EC(50) of 44.6 +/- 1.1 microM and 27.4 +/- 1.1 microM, respectively. Xestospongin B, depending on the dose, suppressed bradykinin-induced Ca(2+) signals in neuroblastoma (NG108-15) cells, and also selectively blocked the slow intracellular Ca(2+) signal induced by membrane depolarization with high external K(+) (47 mM) in rat skeletal myotubes. This slow Ca(2+) signal is unrelated to muscle contraction, and involves IP(3) receptors. In highly purified isolated nuclei from rat skeletal myotubes, Xestospongin B reduced, or suppressed IP(3)-induced Ca(2+) oscillations with an EC(50) = 18.9 +/- 1.35 microM. In rat myotubes exposed to a Ca(2+)-free medium, Xestospongin B neither depleted sarcoplasmic reticulum Ca(2+) stores, nor modified thapsigargin action and did not affect capacitative Ca(2+) entry after thapsigargin-induced depletion of Ca(2+) stores. Ca(2+)-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 IP(3) receptors in cultured rat myotubes, isolated myonuclei, and neuroblastoma (NG108-15) cells.

Dates et versions

hal-00086080 , version 1 (17-07-2006)

Identifiants

Citer

Enrique Jaimovich, César Mattei, José Luis Liberona, Cesar Cárdenas, Manuel Estrada, et al.. Xestospongin B, a competitive inhibitor of IP3-mediated Ca2+ signalling in cultured rat myotubes, isolated myonuclei, and neuroblastoma (NG108-15) cells. FEBS Letters, 2005, 579(10), pp.2051-2057. ⟨10.1016/j.febslet.2005.02.053⟩. ⟨hal-00086080⟩

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