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Xestospongin B, a competitive inhibitor of IP 3 ‐mediated Ca 2+ signalling in cultured rat myotubes, isolated myonuclei, and neuroblastoma (NG108‐15) cells
Author(s) -
Jaimovich Enrique,
Mattei César,
Liberona José Luis,
Cardenas Cesar,
Estrada Manuel,
Barbier Julien,
Debitus Cécile,
Laurent Dominique,
Molgó Jordi
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.02.053
Subject(s) - thapsigargin , myogenesis , depolarization , inositol , endoplasmic reticulum , chemistry , inositol trisphosphate receptor , receptor , inositol trisphosphate , skeletal muscle , biology , endocrinology , biophysics , microbiology and biotechnology , medicine , biochemistry
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 μM and 27.4 ± 1.1 μM, 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 μM. 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.