Effects of the K+ channel blockers paspalitrem-C and paxilline on mammalian smooth muscle.
The tremorgenic alkaloids, paxilline and paspalitrem-C (0.1-10 microM), increased the spontaneous contractility of guinea-pig and rat urinary bladder, and rat duodenum, and induced tension in guinea-pig trachea. These effects are ascribed to blockade of high-conductance, Ca(2+)-activated K+ (BKCa) channels. Paxilline potentiated the charybdotoxin-induced stimulation of guinea-pig detrusor muscle; this is consistent with the alkaloid's ability to allosterically enhance the binding of charybdotoxin to smooth muscle membranes (Knaus et al., 1994). Paspalitrem-C and paxilline did not affect the myogenic activity of isolated portal vein from guinea-pig, which is insensitive to charybdotoxin, or of that from rat which is stimulated by charybdotoxin. Paxilline and paspalitrem-C also differed from charybdotoxin in that the alkaloids did not consistently elicit tension in guinea-pig aortic rings. These discrepancies are attributed to differences in relative potency, sites and/or mechanisms of action of the indole alkaloids vs. peptidyl blockers of the BKCa channel.
DeFarias
F P
FP
Departamento de Bioquímica Médica, ICB, Universidade Federal do Rio de Janeiro, Brazil.
Carvalho
M F
MF
Lee
S H
SH
Kaczorowski
G J
GJ
Suarez-Kurtz
G
G
D000818:Animals; D004347:Drug Interactions; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar
D007211:Indoles; D026902:Potassium Channel Blockers; C048220:paxilline