Jaimovich E. auteur aut IRD Mattei C. auteur aut IRD Liberona J. L. auteur aut IRD Cardenas C. auteur aut IRD Estrada M. auteur aut IRD Barbier J. auteur aut IRD Debitus Cécile auteur aut IRD Laurent Dominique auteur aut IRD Molgo J. auteur aut IRD text journalArticle eng text/pdf reformatted digital access 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. specialized INVERTEBRE AQUATIQUE SUBSTANCE NATURELLE ALCALOIDE STRUCTURE CHIMIQUE ACTIVITE BIOLOGIQUE INTERET PHARMACOLOGIQUE CULTURE CELLULAIRE TEST XESTOSPONGIN B EPONGE xestospongin B inositol 1,4,5 trisphosphate intracellular Ca2+ signals bradykinin neuroblastoma NG108 15 cell rat skeletal myotubes cerebellar membranes isolated myonuclei calcium ATPase NOUVELLE CALEDONIE 035SUBSAN02 579 10 2051-2057 2005 0014-5793 https://www.documentation.ird.fr/hor/fdi:010038253 10.1016/j.febslet.2005.02.053 0014-5793 [F B010038253] https://www.documentation.ird.fr/hor/fdi:010038253 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2024-12/010038253.pdf IRD - Base Horizon / Pleins textes 2006-03-29 2024-12-18 fdi:010038253 fre