ISSN:
1474-8673
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Chemie und Pharmazie
,
Medizin
Notizen:
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.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1474-8673.2004.00314.x
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