Xestospongins: Potent membrane permeable blockers of the inositol 1,4,5- trisphosphate receptor

Juliette Gafni, Julia A. Munsch, Tien H. Lam, Michelle C. Catlin, Lucio G. Costa, Tadeusz F. Molinski, Isaac N. Pessah

Research output: Contribution to journalArticle

477 Scopus citations

Abstract

Xestospongins (Xe's) A, C, D, araguspongine B, and demethylxestospongin B, a group of macrocyclic bis-1-oxaquinolizidines isolated from the Australian sponge, Xestospongia species, are shown to be potent blockers of IP3-mediated Ca2+ release from endoplasmic reticulum vesicles of rabbit cerebellum. XeC blocks IP3-induced Ca2+ release (IC50 = 358 nM) without interacting with the IP3-binding site, suggesting a mechanism that is independent of the IP3 effector site. Analysis of Pheochormocytoma cells and primary astrocytes loaded with Ca2+-sensitive dye reveals that XeC selectively blocks bradykinin- and carbamylcholine-induced Ca2+ efflux from endoplasmic reticulum stores. Xe's represent a new class of potent, membrane permeable IP3 receptor blockers exhibiting a high selectivity over ryanodine receptors. Xe's are a valuable tool for investigating the structure and function of IP3 receptors and Ca2+ signaling in neuronal and nonneuronal cells.

Original languageEnglish (US)
Pages (from-to)723-733
Number of pages11
JournalNeuron
Volume19
Issue number3
DOIs
StatePublished - Sep 1997

ASJC Scopus subject areas

  • Neuroscience(all)

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    Gafni, J., Munsch, J. A., Lam, T. H., Catlin, M. C., Costa, L. G., Molinski, T. F., & Pessah, I. N. (1997). Xestospongins: Potent membrane permeable blockers of the inositol 1,4,5- trisphosphate receptor. Neuron, 19(3), 723-733. https://doi.org/10.1016/S0896-6273(00)80384-0