DIFFERENTIAL-EFFECTS OF 2 CALCIUM-CHANNEL BLOCKERS ON BRONCHIAL SMOOTH-MUSCLE

The effects of the new Ca2+-entry blocker SK&F 96365 (1-{beta- [3- yph enyl)propoxy]-4-methoxy-phenethyl}-1H-imidazole hydrochloride, CAS 130 495-35-1) and nifedipine on the contractile response of guinea-pig tra chea to KCl and histamine are described. Diameter changes of cannulate d, perfused tubes of guinea-pig trachea were recorded by a computerize d video-microscopy bioassay system. In order to determine whether the capacitive calcium entry is the major mechanism in the guinea-pig trac hea, the effects of SK&F 96365, an antagonist of the second-messenger operated channel, were studied. The results of experiments of Ca2+-fre e medium containing EGTA (0.1 mmol l(-1)) indicate that KCl- and hista mine evoked contractions are mainly due to an influx of extracellular Ca2+ rather than due to release from intracellular stores. SK&F 9635 ( 10 mu mol l(-1)) showed a more effective antispasmogenic activity on h istamine-induced contraction of guinea-pig trachea than the voltage-op erated channel (VOC)-blocker nifedipine (10 mu mol 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 9635 in the treatment of asthma.