Abstract
Xestospongins, a group of macrocyclic bis-1-oxaquinolizidines isolated from the Australian sponge, Xestospongia species, are potent blockers of the inositol 1,4,5-trisphosphate (IP(3))-induced Ca2+ release in bi-directional Ca2+-flux conditions. We have now studied the effects of xestospongin C on the (45)Ca2+ uptake and the uni-directional (45)Ca2+ efflux in permeabilized A7r5 smooth-muscle cells. Xestospongin C not only inhibits the IP(3)-induced Ca2+ release, but is also an equally potent blocker of the endoplasmic-reticulum Ca2+ pump, while it has no effect on the passive Ca2+ leak. The inhibition of the IP(3) receptor did not depend on the IP(3), Ca2+ or ATP concentration. Xestospongin C can, therefore, not be considered as a selective blocker of IP(3) receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism
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Calcium Channels / drug effects*
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Calcium Channels / metabolism
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Calcium-Transporting ATPases / antagonists & inhibitors*
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Cell Membrane Permeability / drug effects
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Cells, Cultured
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Dose-Response Relationship, Drug
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Endoplasmic Reticulum / drug effects
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Endoplasmic Reticulum / enzymology*
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Inositol 1,4,5-Trisphosphate Receptors
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Macrocyclic Compounds
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism
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Oxazoles / pharmacology*
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Rats
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Receptors, Cytoplasmic and Nuclear / drug effects*
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Receptors, Cytoplasmic and Nuclear / metabolism
Substances
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Calcium Channels
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Inositol 1,4,5-Trisphosphate Receptors
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Macrocyclic Compounds
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Oxazoles
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Receptors, Cytoplasmic and Nuclear
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xestospongin A
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Calcium-Transporting ATPases
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Calcium