The spasmogenic effect of caffeine in trachealis isolated from control and actively sensitized guinea-pigs

The spasmogenic activity of caffeine (10 mM) was evaluated in tracheal strips obtained from control and sensitized guinea-pigs then pretreated with indomethacin (2.8 microM) and cooled to 20 degrees C. The contraction elicited by caffeine was inhibited by verapamil (100 microM), trifluoperazine (100 and 500 microM) and dantrolene (50 and 500 microM) in the control and the sensitized tissues but was unaffected by disodium cromoglycate (39 microM). However, the same concentration of verapamil produced significantly less inhibition of the caffeine-induced contraction in sensitized compared to control tissues while the reverse was found for trifluoperazine and dantrolene. Exposure to a Ca2+-free, EGTA-containing medium resulted in 33% inhibition of the response to caffeine in control tissues but no inhibition in sensitized tissues. These results suggest the existence of differences in calcium movements in response to caffeine between control and sensitized tissues that may reflect abnormalities in calcium handling by the sensitized tissue.