Xestospongin C is an equally potent inhibitor of the inositol 1,4,5-trisphosphate receptor and the endoplasmic-reticulum Ca(2+) pumps

Cell Calcium. 1999 Jul-Aug;26(1-2):9-13. doi: 10.1054/ceca.1999.0047.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Calcium-Transporting ATPases / antagonists & inhibitors*
  • Cell Membrane Permeability / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / enzymology*
  • Inositol 1,4,5-Trisphosphate Receptors
  • Macrocyclic Compounds
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Oxazoles / pharmacology*
  • Rats
  • Receptors, Cytoplasmic and Nuclear / drug effects*
  • Receptors, Cytoplasmic and Nuclear / metabolism

Substances

  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Macrocyclic Compounds
  • Oxazoles
  • Receptors, Cytoplasmic and Nuclear
  • xestospongin A
  • Calcium-Transporting ATPases
  • Calcium