Ca2+-entry blockade by CAF603, a carotane sesquiterpene isolated from Trichoderma virens.
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].
Suarez-Kurtz
G
G
Departamento de Bioquímica Médica, ICB, Universidade Federal do Rio de Janeiro, Brazil. kurtz@server.bioqmed.ufrj.br
Nascimento
J H
JH
Ondeyka
J G
JG
Kaczorowski
G J
GJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011817:Rabbits; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014242:Trichoderma / Q000737:chemistry*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D010455:Peptides; D026902:Potassium Channel Blockers; D012717:Sesquiterpenes; C067644:CAF 603; C064719:iberiotoxin; D005905:Glyburide