Effect of toluene diisocyanate on beta adrenergic receptor function. Biochemical and physiologic studies

The effects of toluene diisocyanate (TDI) on beta adrenergic receptor function was investigated using 2 different experimental model systems: (1) a biochemical model measured beta adrenergic adenylate cyclase activity of frog erythrocytes and (2) guinea pig tracheal smooth muscle responsiveness after in vivo exposure was used to assess physiologic function. The TDI inhibited isoproterenol-stimulated erythrocyte adenylate cyclase activity in a dose-dependent manner. Similar results were obtained with fluoride-ion-stimulated activity, suggesting that TDI caused a nonspecific inhibition of adenylate cyclase activity. No difference in tracheal smooth muscle responsiveness, measured as the concentration of isoproterenol corresponding to 50% of maximal relaxation (ED50), was observed in TDI-exposed (9.36 +/- 0.11 SE) guinea pigs when compared with control (9.38 +/- 0.06 SE) animals, nor was there a difference in the degree of maximal relaxation induced by isoproterenol. The differences between the in vitro cell studies and the tracheal smooth muscle investigations suggest that mechanisms other than direct beta adrenergic blockade should be considered in TDI-induced asthma.