Relaxation of cat trachea by β‐adrenoceptor agonists can be mediated by both β1‐ and β2‐adrenoceptors and potentiated by inhibitors of extraneuronal uptake

Abstract

1 Responses (relaxation) to the β-adrenoceptor agonists, isoprenaline, fenoterol or noradrenaline, were obtained on cat tracheal preparations contracted with a submaximal concentration of carbachol (0.5 μm). 2 The relative potencies of isoprenaline: fenoterol: noradrenaline were 100:8.1:10.7. From this, it was concluded that responses were mediated predominantly by β₁-adrenoceptors but that a minor population of β₂-adrenoceptors might also be involved. 3 Schild plots for the selective antagonists atenolol (β₁-selective) or ICI 118, 551 (β₂-selective) were in different locations, i.e. were separated, depending on whether the antagonist was antagonizing noradrenaline or fenoterol. This supported the conclusion that β₂- as well as β₁-adrenoceptors were involved in mediating the response. In this respect, cat trachea resembles cat atria (rate responses). 4 In the presence of atenolol the concentration-response curves to fenoterol became biphasic. This was interpreted as indicating that the β₂-adrenoceptors were too few in number to elicit a maximum tissue response. 5 Responses to isoprenaline of cat trachea were potentiated by the extraneuronal uptake inhibitor drugs, corticosterone and metanephrine. This indicated that extraneuronal uptake could modulate β-adrenoceptor-mediated responses (relaxation) of cat trachea. 6 Cat trachea resembles guinea-pig trachea in that (i) the β-adrenoceptor population mediating relaxation is mixed (β₁ + β₂) and (ii) responses to isoprenaline are modulated by its extraneuronal uptake. However, cat trachea differs from guinea-pig trachea in that the predominant β-adrenoceptor sub-type is β₁ not β₂.