Beta adrenoceptor binding and induced relaxation in airway smooth muscle from patients with chronic airflow obstruction.

Abstract

Beta adrenoceptor function in central airway smooth muscle of patients with chronic airflow obstruction was investigated by radioligand binding studies and isoprenaline relaxation experiments. Receptor characteristics were determined in tracheal smooth muscle preparations obtained at necropsy from 12 patients and in bronchial tissue obtained at thoracotomy from 21 patients with chronic airflow obstruction. Receptor characteristics were compared with those obtained in airway tissue preparations from 65 control subjects without chronic airflow obstruction. The number ofbeta adrenoceptors, their binding affinity for the radioligand ['25I]-(-)-cyanopindolol, and the tissue binding characteristics of isoprenaline were similar in tissue from patients with chronic airflow obstruction and from control subjects. Isoprenaline induced relaxation of tracheal smooth muscle without precontraction by methacholine showed slightly (though not significantly) less sensitivity to isoprenaline in patients with chronic airflow obstruction than in control subjects (mean (SEM) pD2-the negative logarithm of the concentration producing 50% relaxation--632 (0'16) v 6-62 (0 15)). The same pattern of pD2 values was found in segmental bronchial strips without precontraction by methacholine (chronic airflow obstruction 655 (0'27), control 7 14 (0'12)). Isoprenaline relaxation in segmental bronchial strips when contracted maximally was significantly less in the patients with airflow obstruction than in the control subjects (pD2 value 5'99 (0-18) v 6'45 (0'07)). These results suggest that beta adrenoceptors in airway smooth muscle of patients with chronic airflow obstruction are not abnormal in number or in binding affinity but that there is less effective coupling between components of the relaxant system distal to the beta adrenoceptor. The possibility that the reduced isoprenaline sensitivity is a consequence of previous bronchodilator treatment cannot be excluded.

Equine recurrent airway obstruction does not alter airway muscarinic acetylcholine receptor expression and subtype distribution

“…However, in the latter case, there was a statistically significant diminution (∼70%) of the mAChR density. On the other hand, our present data contrast the slight but not significant increase (8–25%) in total number of mAChR in central and segmental airway smooth muscle of patients suffering from chronic and severe airflow obstruction (van Koppen et al. , 1989).…”

“…For example, in the human asthmatic lungs, neither alterations (Haddad et al. , 1996), nor an increase (van Koppen et al. , 1989) in total number of postsynaptic mAChR was observed.…”

“…Although the reasons behind these defective mechanisms remain to be elucidated, it was assumed that changes in the expression of mAChR might occur in obstructive airway diseases depending on how frequently bronchial hyper-reactivity is observed (Coulson & Fryer, 2003). For example, in the human asthmatic lungs, neither alterations (Haddad et al, 1996), nor an increase (van Koppen et al, 1989) in total number of postsynaptic mAChR was observed. Accordingly, in asthmatic patients an increase in cholinergic contraction was associated with enhanced M 3receptor function (de Jongste et al, 1987a;Bai, 1990), but in various patients with chronic obstructive pulmonary diseases (COPD) no change was observed (de Jongste et al, 1987b;van Koppen et al, 1988).…”

Beta2 adrenergic receptors in asthma: A current perspective

“…As an alternative, other adjacent receptor-mediated events, acting via protein kinase C, may be involved, that is, via receptor crosstalk (see section on densensitization). Furthermore, the /3AR-mediated relaxant abnormality may not be unique to asthma, since similar changes were seen in airway smooth muscle from subjects with COPD in the study by Van Koppen discussed above [77].…”

“…Without precontraction with methacholine, no differences were seen in/3AR agonist-medicated relaxation. However, following precontraction airways from patients with COPD but not normal airways showed a one-half log-dose decrease in responsiveness [77]. Whicker et al [81] studied airway smooth muscle under conditions of intrinsic tone only, whereas Svedmyr et al [73] and Cerrina et al [14] precontracted tissues with cholinergic agonists and histamine, respectively.…”