Evidence showing that β‐adrenoceptor subtype responsible for the relaxation induced by isoprenaline is principally β2 but not β1 in guinea‐pig tracheal smooth muscle

1. The present study was carried out to pharmacologically identify the beta-adrenoceptor subtype that mediates isoprenaline-elicited relaxation in the isolated guinea-pig tracheal smooth muscle, to answer the question whether it is beta(1)- or beta(2)-subtype? 2. Isoprenaline as well as salbutamol, a well-known beta(2)-selective adrenoceptor agonist, produced a concentration-dependent relaxation with a pD(2) value of 8.12 vs. 7.54 for salbutamol. 3. Isoprenaline-elicited relaxation was not affected by beta(1)-selective antagonists, atenolol and CGP-20,712A, within the concentration ranges supposed to antagonize beta(1)-subtype: atenolol, < or =10(-6) M; CGP-20,712A, < or =10(-8) M. 4. By contrast, the concentration-response curves for isoprenaline as well as salbutamol were shifted rightwards in a competitive fashion by atenolol at the concentrations > or =3 x 10(-6) M. However, pA(2) values of atenolol against isoprenaline (5.86) and salbutamol (5.71) were consistent with the value corresponding to beta(2)- but not to beta(1)-subtype (around 7.00), and these values were not significantly different from each other. 5. Competitive antagonism of the relaxations to isoprenaline and salbutamol were also obtained with beta(2)-selective antagonists, butoxamine and ICI-118,551. Against isoprenaline and salbutamol, the pA(2) values of butoxamine (6.51 vs. 6.81) and ICI-118,551 (8.83 vs. 8.90) were substantially identical. Thus the primary mediation of beta(2)-receptor in the relaxations was strongly supported. 6. The present findings provide evidence that the beta-adrenoceptor which mediates isoprenaline-elicited relaxation of guinea-pig tracheal smooth muscle is essentially beta(2)- but not beta(1)-subtype. The present study also indicates the importance of using multiple receptor antagonists with different pA(2) values to pharmacologically identify the responsible receptor subtype in smooth muscle mechanical responses.