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. 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 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. 2005 text https://www.documentation.ird.fr/hor/fdi:010038253 fdi:010038253 Jaimovich E., Mattei C., Liberona J. L., Cardenas C., Estrada M., Barbier J., Debitus Cécile, Laurent Dominique, Molgo J.. Xestospongin B, a competitive inhibitor of IP3-mediated Ca2+ signalling in cultured rat myotubes, isolated myonuclei, and neuroblastoma (NG108-15) cells. 2005, 579 (10), 2051-2057 EN NOUVELLE CALEDONIE