[Effects of toxins, apamine, charybdotoxin and iberiotoxin on the relaxation of the smooth muscular fiber induced by imidazo(1,2-a)pyrazine derivative].
Experiments have been performed in order to analyse the mechanism whereby SCA40, a new imidazo[1,2-a]pyrazine derivative relaxes airway smooth muscle. We investigated the effect of different toxins, known to be K(+)-channel blockers on guinea-pig smooth muscle relaxant activity of SCA40. The small conductance Ca(2+)-activated K(+)-channel blocker apamin (100 nM) did not antagonize the relaxant activity of SCA40 in 1 microM carbachol-contracted isolated guinea pig trachea. The large conductance Ca(2+)-activated K(+)-channel blocker, iberiotoxin (30, 60 and 180 nM) antagonized the relaxant activity of SCA40 in an apparently competitive manner. The concentration-relaxation curves to SCA40 were shifted to the right with no significant alteration in the maximum response. The relaxant activity of SCA40 in 1 microM carbachol-contracted isolated trachea was antagonized by both charybdotoxin (60 nM) and iberiotoxin (60 nM), but the antagonism induced by iberiotoxin appears to be more potent than that induced by charybdotoxin. It is concluded that the potent relaxant activity of SCA40 on guinea-pig airway smooth muscle in vitro involves a charybdotoxin and iberiotoxin sensitive K(+)-channel.
Laurent
F
F
Laboratoire de Pharmacodynamie, URA CNRS 1111, Faculté de Pharmacie, Montpellier.
Michel
A
A
Bonnet
P A
PA
Bompart
J
J
Chapat
J P
JP
Boucard
M
M
D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D018999:Charybdotoxin; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D012604:Scorpion Venoms / Q000494:pharmacology*; D014132:Trachea
D007093:Imidazoles; D010276:Parasympatholytics; D010455:Peptides; D015221:Potassium Channels; D011719:Pyrazines; D012604:Scorpion Venoms; D018999:Charybdotoxin; C080660:6-bromo-8-methylaminoimidazo(1,2-a)pyrazine-2-carbonitrile; D001030:Apamin; C064719:iberiotoxin