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 language | English (US) |
|---|---|
| Pages (from-to) | 723-733 |
| Number of pages | 11 |
| Journal | Neuron |
| Volume | 19 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1997 |
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ASJC Scopus subject areas
- Neuroscience(all)
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Xestospongins : Potent membrane permeable blockers of the inositol 1,4,5- trisphosphate receptor. / Gafni, Juliette; Munsch, Julia A.; Lam, Tien H.; Catlin, Michelle C.; Costa, Lucio G.; Molinski, Tadeusz F.; Pessah, Isaac N.
In: Neuron, Vol. 19, No. 3, 09.1997, p. 723-733.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Xestospongins
T2 - Potent membrane permeable blockers of the inositol 1,4,5- trisphosphate receptor
AU - Gafni, Juliette
AU - Munsch, Julia A.
AU - Lam, Tien H.
AU - Catlin, Michelle C.
AU - Costa, Lucio G.
AU - Molinski, Tadeusz F.
AU - Pessah, Isaac N.
PY - 1997/9
Y1 - 1997/9
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0030964614&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(00)80384-0
DO - 10.1016/S0896-6273(00)80384-0
M3 - Article
C2 - 9331361
AN - SCOPUS:0030964614
VL - 19
SP - 723
EP - 733
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 3
ER -