Ca2+-entry blockade by CAF603, a carotane sesquiterpene isolated from Trichoderma virens

Eur J Pharmacol. 1997 Sep 24;335(2-3):153-9. doi: 10.1016/s0014-2999(97)01206-5.

Abstract

Isometric tension recordings and patch-clamp methods were combined to explore the functional effects and mechanisms of action of 8-daucene-3,4-diol (CAF603), a carotane sesquiterpene isolated from the fungus Trichoderma virens. CAF603 (1-100 microM) inhibited the spontaneous motility of guinea-pig portal vein, duodenum and ileum, and the Ca2+-induced tension of depolarized ileum strips. These effects were not antagonized by either iberiotoxin or glyburide. CAF603 increased the spontaneous motility of guinea-pig detrusor muscle, but inhibited the contraction induced by high-KCl, depolarizing salines. CAF603 blocked L-type Ca2+ channel currents of rabbit cardiac myocytes. It is proposed that Ca2+-entry blockade accounts for the inhibitory effects of CAF603 on smooth muscle contractility, whereas the stimulation of spontaneous motility of detrusor muscle is ascribed to blockade of Ca2+-activated K+ (BKCa) channel currents. The latter interpretation is consistent with the allosteric modulation of charybdotoxin binding to BKCa in smooth muscle membranes [Lee et al., 1995. J. Nat. Prod. 58, 1822-1828].

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channel Blockers / isolation & purification
  • Calcium Channel Blockers / pharmacology*
  • Glyburide / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Intestine, Small / drug effects
  • Intestine, Small / physiology
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle Tonus / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Myocardium / cytology
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Potassium Channel Blockers
  • Rabbits
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Trichoderma / chemistry*
  • Urinary Bladder / drug effects
  • Urinary Bladder / physiology

Substances

  • Calcium Channel Blockers
  • Peptides
  • Potassium Channel Blockers
  • Sesquiterpenes
  • CAF 603
  • iberiotoxin
  • Glyburide