Comparison of Functional β-Adrenoceptor Heterogeneity in Central and Peripheral Airway Smooth Muscle of Guinea Pig and Man

Abstract

The nature of the β-adrenoceptor population(s) mediating the relaxation of guinea pig and human airway smooth muscle was investigated. On the basis of a preferential blockade by β₁ and β₂ selective antagonists of the relaxation induced by β₁ and β₂- selective agonists, guinea pig tracheal strip relaxation was found to be mediated both by β₁ - and β₂ - adrenoceptors, the relative participation of which depending on the relative affinities of the agonist towards these two receptors. With highly selective antagonists the noradrenaline(NA)-induced relaxation could be split up biphasically into a β₁- and a β₂ - component. In contrast, no such differential blockade was observed with the guinea pig lung parenchyma strip relaxation which is mediated by a homogenous β₂ -adreno-ceptor population. On comparison of the tracheal, the spirally cut main bronchus- and intrapulmonary airway smooth muscle strips it could be shown that both the sensitivity of NA for neuronal uptake and the apparent affinity of the relaxation by NA decreased in the direction of the lung periphery. Using the same techniques it was ascertained that the relaxation of human tracheal smooth muscle (autopsy, obtained within 6 hours after death), main bronchus and intrapulmonary smooth muscle (operation) are mediated by homogenous β₂ -adrenoceptor populations. In addition, neuronal and extraneuron-al uptake sites were not operative in these preparations, whether obtained from operation or from autopsy.