Classification of beta-adrenoceptors in ferret tracheal smooth muscle by pharmacological responses

Abstract

Beta-adrenoceptors in ferret tracheal smooth muscle were classified into beta 1 or beta 2 by determination of (i) the potency rank order for isoprenaline, noradrenaline and adrenaline, and (ii) apparent pA2-values for a specific beta 1-antagonist (practolol) and a specific beta 2-antagonist (ICI 118.551) and (iii) concentration-inhibition curves for procaterol, a beta-agonist showing a biphasic concentration-response curve in organs with a mixed beta 1 and beta 2 adrenoceptor population. We used in vitro tracheal rings and assessed the responses to beta-adrenoceptor agonists as inhibition of phasic contractions elicited by electrical field stimulation (2 Hz for 20 s) or relaxation of tonic contractions elicited by acetylcholine (0.5 microM). The potency rank order for the agonists was isoprenaline greater than noradrenaline approximately adrenaline indicating action through beta 1-receptors. Apparent pA2-values for the antagonists were for 1, 3 and 10 microM practolol 6.0 (SE 0.27), 6.1 (SE 0.21) and 6.3 (SE 0.03), respectively. Apparent pA2 for 0.1, 1 and 10 microM ICI 118.551 were 6.8 (SE 0.25), 6.7 (SE 0.12) and 6.1 (SE 0.14), respectively. These values agree well with published pA2-values for the action of these drugs on beta 1-adrenoceptors. However, the Schild plot for ICI 118.551 was alinear indicating a possible heterogeneity of the beta-adrenoceptors in ferret trachea. The concentration-response curve for procaterol showed the biphasic form typical for organs with a mixed beta 1 and beta 2 population. However, the lower part of the curve, reflecting stimulation of beta 2-adrenoceptors reached only 17.5% (SE 1.4) of the maximally achieved inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)