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

  • Jaimovich, E.
  • Mattei, C.
  • Liberona, J. L.
  • Cardenas, C.
  • Estrada, M.
  • Barbier, J.
  • Debitus, Cécile
  • Laurent, Dominique
  • Molgo, J.
Publication Date
Jan 01, 2005
Horizon / Pleins textes
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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 [H-3]IP3 from both rat cerebellar membranes and rat skeletal myotube homogenates with an EC50 of 44.6 +/- 1.1 mu M and 27.4 +/- 1.1 mu M, 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 +/- 1.35 mu M. In rat my rotubes 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 myrotube 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. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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