ISSN:
1474-8673
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
1 The present study was carried out to pharmacologically identify the β-adrenoceptor subtype that mediates isoprenaline-elicited relaxation in the isolated guinea-pig tracheal smooth muscle, to answer the question whether it is β1- or β2-subtype? 2 Isoprenaline as well as salbutamol, a well-known β2-selective adrenoceptor agonist, produced a concentration-dependent relaxation with a pD2 value of 8.12 vs. 7.54 for salbutamol. 3 Isoprenaline-elicited relaxation was not affected by β1-selective antagonists, atenolol and CGP-20,712A, within the concentration ranges supposed to antagonize β1-subtype: atenolol, ≤10−6 m; CGP-20,712A, ≤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 ≥3 × 10−6 m. However, pA2 values of atenolol against isoprenaline (5.86) and salbutamol (5.71) were consistent with the value corresponding to β2- but not to β1-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 β2-selective antagonists, butoxamine and ICI-118,551. Against isoprenaline and salbutamol, the pA2 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 β2-receptor in the relaxations was strongly supported. 6 The present findings provide evidence that the β-adrenoceptor which mediates isoprenaline-elicited relaxation of guinea-pig tracheal smooth muscle is essentially β2- but not β1-subtype. The present study also indicates the importance of using multiple receptor antagonists with different pA2 values to pharmacologically identify the responsible receptor subtype in smooth muscle mechanical responses.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1474-8673.2004.00314.x
Permalink
