Relaxation of cat trachea by beta-adrenoceptor agonists can be mediated by both beta1- and beta2-adrenoceptors and potentiated by inhibitors of extraneuronal uptake.

Abstract

1--Responses (relaxation) to the beta-adrenoceptor agonists, isoprenaline, fenoterol or noradrenaline, were obtained on cat tracheal preparations contracted with a submaximal concentration of carbachol (0.5 microM). 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 beta 1-adrenoceptors but that a minor population of beta 2-adrenoceptors might also be involved. 3--Schild plots for the selective antagonists atenolol (beta 1-selective) or ICI 118,551 (beta 2-selective) were in different locations, i.e. were separated, depending on whether the antagonist was antagonizing noradrenaline or fenoterol. This supported the conclusion that beta 2- as well as beta 1-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 beta 2-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 beta-adrenoceptor-mediated responses (relaxation) of cat trachea. 6--Cat trachea resembles guinea-pig trachea in that (i) the beta-adrenoceptor population mediating relaxation is mixed (beta 1 + beta 2) and (ii) responses to isoprenaline are modulated by its extraneuronal uptake. However, cat trachea differs from guinea-pig trachea in that the predominant beta-adrenoceptor sub-type is beta 1 not beta 2.