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

Abstract

The nature of the beta-adrenoceptor population(s) mediating the relaxation of guinea pig and human airway smooth muscle was investigated. On the basis of a preferential blockade by beta 1- and beta 2-selective antagonists of the relaxation induced by beta 1- and beta 2-selective agonists, guinea pig tracheal strip relaxation was found to be mediated both by beta 1- and beta 2-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 beta 1- and a beta 2-component. In contrast, no such differential blockade was observed with the guinea pig lung parenchyma strip relaxation which is mediated by a homogenous beta 2-adrenoceptor 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 beta 2-adrenoceptor populations. In addition, neuronal and extraneuronal uptake sites were not operative in these preparations, whether obtained from operation or from autopsy.

Effects of Noradrenaline on the Isolated Human Bronchus. Comparison With the Isolated Guinea Pig Trachea

“…The relaxant activity of noradrenaline in human bronchi that we observed was comparable to that observed by Zaagsma et al (1983) who, working on human bronchi obtained post mortem, reported a -log EC,, of 4.60 for noradrenaline, or to the findings of Goldie et al (1984) in human tissue also obtained by autopsy; these authors reported EC,, of 2.02 z t 0.27 and 2.81 k 0.82 pM, respectively, of noradrenaline in preparations under resting tone or precontracted with carbachol to 50% of maximal tension.…”

Rosiglitazone elicits in vitro relaxation in airways and precision cut lung slices from a mouse model of chronic allergic airways disease

“…Consistent with our previous findings in PCLS (3), RGZ was able to maintain potency and elicit marked relaxation in maximally contracted trachea, overcoming the functional antagonism shown to limit ␤-adrenoceptor responsiveness (19). Dilator responses mediated through ␤ 2 -adrenoceptors in guinea pig trachea may be of greater relevance to human airways (23,36). The higher potency and efficacy of SALB in tracheal segments from guinea pigs relative to mice are consistent with this, while the finding of marked relaxation to RGZ at similar potency in both species is suggestive of potential benefit independent of ␤-adrenoceptor density.…”

Selective and full β1‐adrenoceptor agonist action of a catechol derivative of denopamine (T‐0509) in the guinea‐pig cardiac muscle and trachea: comparison with denopamine, xamoterol and isoprenaline

“…However, P3-adrenoceptorstimulation has been reported to relax spontaneous tone in the guinea-pig trachea (Zaagsma et al, 1983;Lemoine et al, 1989b). In the present study, T-0509, in contrast to the cardiac muscle, exhibited a relaxant action with a potency 38 times less than isoprenaline through 132-adrenoceptors in the histamine-contracted trachea, but with a similar intrinsic activity to isoprenaline.…”