Inhibitory mechanism of xestospongin-C on contraction and ion channels in the intestinal smooth muscle

Br J Pharmacol. 2002 Dec;137(8):1207-12. doi: 10.1038/sj.bjp.0704988.


1. Xestospongin-C isolated from a marine sponge, Xestospongia sp., has recently been shown to be a membrane-permeable IP(3) receptor inhibitor. In this study we examined the effects of this compound on smooth muscle from guinea-pig ileum. 2. In guinea-pig ileum permeabilized with alpha-toxin, xestospongin-C (3 microM) inhibited contractions induced by Ca(2+) mobilized from sarcoplasmic reticulum (SR) with IP(3) or carbachol with GTP, but not with caffeine. 3. In intact smooth muscle tissue, xestospongin-C (3-10 microM) inhibited carbachol- and high-K+-induced increases in [Ca(2+)](i) and contractions at sustained phase. 4. It also inhibited voltage-dependent inward Ba(2+) currents in a concentration-dependent manner with an IC(50) of 0.63 microM. Xestospongin-C (3-10 microM) had no effect on carbachol-induced inward Ca(2+) currents via non-selective cation channels; but it did reduce voltage-dependent K+ currents in a concentration-dependent manner with an IC(50) of 0.13 microM. 5. These results suggest that xestospongin-C inhibits the IP(3) receptor but not the ryanodine receptor in smooth muscle SR membrane. In intact smooth muscle cells, however, xestospongin-C appears to inhibit voltage-dependent Ca(2+) and K+ currents at a concentration range similar to that at which it inhibits the IP(3) receptor. Xestospongin-C is a selective blocker of the IP(3) receptor in permeabilised cells but not in cells with intact plasma membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / physiology
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Ileum / drug effects*
  • Ileum / physiology
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ion Channels / antagonists & inhibitors
  • Ion Channels / physiology*
  • Macrocyclic Compounds
  • Male
  • Muscle Contraction / drug effects*
  • Muscle Contraction / physiology
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Oxazoles / isolation & purification
  • Oxazoles / pharmacology*
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / physiology


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