Differential effects of two calcium channel blockers on bronchial smooth muscle.
The effects of the new Ca(2+)-entry blocker SK&F 96365 (1-¿beta-[4-methoxyphenyl)propoxy]-4-methoxy-phenethyl¿-1H- imidazole hydrochloride, [sequence: see text] CAS 130495-35-1) and nifedipine on the contractile response of guinea-pig trachea to KCl and histamine are described. Diameter changes of cannulated, perfused tubes of guinea-pig trachea were recorded by a computerized video-microscopy bioassay system. In order to determine whether the capacitive calcium entry is the major mechanism in the guinea-pig trachea, the effects of SK&F 96365, an antagonist of the second-messenger operated channel, were studied. The results of experiments in Ca(2+)-free medium containing EGTA (0.1 mmol l-1) indicate that KCl- and histamine evoked contractions are mainly due to an influx of extracellular Ca2+ rather than due to release from intracellular stores. SK&F 96365 (10 mumol l-1) showed a more effective antispasmogenic activity on histamine-induced contraction of guinea-pig trachea than the voltage-operated channel (VOC)-blocker nifedipine (10 mumol l-1). Nifedipine is only effective in inhibiting KCl induced contraction. These results may have significance for the use of agents such as SK&F 96365 in the treatment of asthma.
Baersch
G
G
Department of Clinical Pharmacology, Hannover Medical School, Germany.
Frölich
J C
JC
D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D015290:Second Messenger Systems / Q000187:drug effects
D002121:Calcium Channel Blockers; D007093:Imidazoles; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D002118:Calcium