A COMPARISON BETWEEN CLENBUTEROL, SALBUTAMOL AND TERBUTALINE IN RELATION TO RECEPTOR-BINDING AND IN-VITRO RELAXATION OF EQUINE TRACHEAL MUSCLE

Beta(2)-adrenoceptor agonists are used as bronchodilators in both huma ns and horses. Of these drugs, clenbuterol is the one most frequently used when treating chronic obstructive pulmonary disease in the horse, while salbutamol and terbutaline are used in the treatment of human a sthma, Little is known of the properties of the latter two drugs in eq uine medicine. We have compared salbutamol and terbutaline with clenbu terol in relation to their ability to relax muscle strips from equine tracheal muscle, precontracted with 40 nM carbachol, in tissue chamber s, The affinities of these drugs to the beta(2)-adrenoceptors in homog enates of the same muscle tissue were also examined. These experiments were performed with radioligand binding studies using the very potent beta-adrenoceptor antagonist I-125-cyanopindolol. The three drugs wer e almost equipotent in relaxing the muscle strips. The EC50-values for salbutamol, terbutaline and clenbuterol were 5.6, 13.8 and 2.1 nM, re spectively, and all three drugs relaxed the preparations completely. I n the competitive binding study, however, the K-d-value of clenbuterol was much lower (24 nM) than that of salbutamol and terbutaline (1100 nM and 3900 nM, respectively). The amount of receptors bound at the EC 50-value of clenbuterol was 8% compared to less than 1% for salbutamol and terbutaline. This indicates a lower intrinsic efficacy of clenbut erol than of the other two drugs. The beta-adrenoceptor density was 45 +/- 14.3 fmol/mg protein (mean +/- SD) and the K-d-value of I-125-cya nopindolol was 11.4 +/- 3.3 pM.