INVITRO TACHYPHYLAXIS TO ISOPRENALINE IN GUINEA-PIG TRACHEA - INFLUENCE OF THEOPHYLLINE

We used frontally opened tracheal rings, contracted with 10-mu-M of histamine to produce beta-adrenoceptor tachyphylaxis by isoprenaline incubation and to evaluate whether theophylline can prevent this tachyphylaxis. Two concentration-response experiments with isoprenaline were performed in each ring. Between the concentration-response experiments the rings were incubated using four different treatments, isoprenaline (3-mu-M), theophylline (1 mM), theophylline + isoprenaline or vehicle for 60 min. Tachyphylaxis was evaluated as the difference in pD2 (-log EC50) during the first and second concentration-response experiment. Isoprenaline incubation produced a shift to the right of the concentration-response curve. The shift was small (approximately 0.2 log units) but significantly different from the control group. Theophylline failed to influence the process either alone or in combination with isoprenaline. In conclusion, beta-adrenoceptor tachyphylaxis after isoprenaline incubation in isolated guinea-pig trachea proved to be a very small effect and we observed no influence by theophylline.