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Paxilline

 
7: Eur J Pharmacol. 1996 Oct 24;314(1-2):123-8.  

 

Effects of the K+ channel blockers paspalitrem-C and paxilline on mammalian smooth muscle.



DeFarias FP, Carvalho MF, Lee SH, Kaczorowski GJ, Suarez-Kurtz G.

Departamento de Bioquimica Medica, ICB, Universidade Federal do Rio de Janeiro, Brazil.

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.

PMID: 8957227 [PubMed - indexed for MEDLINE]


 

 




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