@article{fdi:010038253, title = {{X}estospongin {B}, a competitive inhibitor of {IP}3-mediated {C}a2+ signalling in cultured rat myotubes, isolated myonuclei, and neuroblastoma ({NG}108-15) cells}, author = {{J}aimovich, {E}. and {M}attei, {C}. and {L}iberona, {J}. {L}. and {C}ardenas, {C}. and {E}strada, {M}. and {B}arbier, {J}. and {D}ebitus, {C}{\'e}cile and {L}aurent, {D}ominique and {M}olgo, {J}.}, editor = {}, language = {{ENG}}, abstract = {{X}estospongin {B}, a macrocyclic bis-1-oxaquinolizidine alkaloid extracted from the marine sponge {X}estospongia exigua, was highly purified and tested for its ability to block inositol 1,4,5-trisphosphate ({IP}3)-induced {C}a2+ release. {I}n a concentration-dependent manner xestospongin {B} displaced [{H}-3]{IP}3 from both rat cerebellar membranes and rat skeletal myotube homogenates with an {EC}50 of 44.6 +/- 1.1 mu {M} and 27.4 +/- 1.1 mu {M}, respectively. {X}estospongin {B}, depending on the dose, suppressed bradykinin-induced {C}a2+ signals in neuroblastoma ({NG}108-15) cells, and also selectively blocked the slow intracellular {C}a2+ signal induced by membrane depolarization with high external {K}+ (47m{M}) in rat skeletal myotubes. {T}his slow {C}a2+ signal is unrelated to muscle contraction, and involves {IP}3 receptors. {I}n highly purified isolated nuclei from rat skeletal myotubes, {X}estospongin {B} reduced, or suppressed {IP}3-induced {C}a2+ oscillations with an {EC}50 = 18.9 +/- 1.35 mu {M}. {I}n rat my rotubes exposed to a {C}a2+-free medium, {X}estospongin {B} neither depleted sarcoplasmic reticulum {C}a2+ stores, nor modified thapsigargin action and did not affect capacitative {C}a2+ entry after thapsigargin-induced depletion of {C}a2+ stores. {C}a2+-{ATP}ase activity measured in skeletal myrotube homogenates remained unaffected by {X}estospongin {B}. {I}t is concluded that xestospongin {B} is an effective cell-permeant. competitive inhibitor of {IP}3 receptors in cultured rat myotubes, isolated myonuclei, and neuroblastoma ({NG}108-15) cells. (c) 2005 {F}ederation of {E}uropean {B}iochemical {S}ocieties. {P}ublished by {E}lsevier {B}.{V}. {A}ll rights reserved.}, keywords = {{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 {C}a2+ signals ; bradykinin ; neuroblastoma {NG}108 15 cell ; rat skeletal myotubes ; cerebellar membranes ; isolated myonuclei ; calcium {ATP}ase ; {NOUVELLE} {CALEDONIE}}, booktitle = {}, journal = {{F}ebs {L}etters}, volume = {579}, numero = {10}, pages = {2051--2057}, ISSN = {0014-5793}, year = {2005}, DOI = {10.1016/j.febslet.2005.02.053}, URL = {https://www.documentation.ird.fr/hor/fdi:010038253}, }