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  • Title: Ca2+-entry blockade by CAF603, a carotane sesquiterpene isolated from Trichoderma virens.
    Author: Suarez-Kurtz G, Nascimento JH, Ondeyka JG, Kaczorowski GJ.
    Journal: Eur J Pharmacol; 1997 Sep 24; 335(2-3):153-9. PubMed ID: 9369368.
    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].
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