Adrenoceptor Status in Bronchial Asthma

Titinchi, Saad Jaber (1985) Adrenoceptor Status in Bronchial Asthma. PhD thesis, University of Glasgow.

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The aim of this thesis was to investigate a long-standing hypothesis (Szentivanyi, 1968) that the underlying aetiology of atopic diseases (particularly bronchial asthma) may have a component related to beta-adrenoceptor defects. Later (Szentivanyi, 1979) this hypothesis was modified to include a possible imbalance of the alpha:beta adrenoceptor ratio Patients with asthma have marked circadian variation in bronchomotor tone, often demonstrated as the morning dip in FEV1. In terms of the above hypothesis, this could result from changes in adrenoceptor kinetics. Equally, the "dip" might be related to other humoral circadian rhythms. Owing to problems in obtaining human lung tissue this study, in accord with many others, used human lymphocytes as the target tissue for adrenoceptor investigations. Beta2-adrenoceptor kinetics were studied using radioligand binding techniques in both normals and asthmatic patients (extrinsic) at 0800 h and 1800 h. In addition, the effects of orally administered salbutamol were followed at similar times. Any disparity in the adrenoceptor kinetics of the control/asthmatic groups would support Szentivanyi's hypothesis. A significant circadian variation in beta2-adrenoceptor number was observed in both groups. The expected down-regulation of the receptors occurred in both groups on administration of salbutamol, but the circadian rhythm persisted although its magnitude was reduced. Both groups appeared to compensate the down-regulation by increasing receptor affinity. At no point in the study were the results for the two groups statistically significantly different. In a second study, both beta2- and alpha2-adrenoceptor kinetics were studied under similar conditions to the first study. In addition, the ratio of alpha2:beta2 adrenoceptors was followed to see if any shifts occurred, particularly in the asthmatic group. The beta2 results were statistically similar to the first study. The kinetics of the alpha2-adrenoceptors remained constant throughout the study, i.e. they did not show a circadian variation and were not affected by salbutamol administration. Although there was a significant difference in the alpha2:beta2 ratio at 0800 h and 1800 h, this related solely to the circadian variation and/or down-regulation of the beta2-adrenoceptors. In conclusion, this study produces no evidence to support Szentivanyi's hypothesis. Receptor function in the asthmatic groups was remarkably similar to that of the control group. Neither was there any evidence for a beta to alpha shift in asthmatic patients.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Medicine, Immunology
Date of Award: 1985
Depositing User: Enlighten Team
Unique ID: glathesis:1985-77413
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 09:09
Last Modified: 14 Jan 2020 09:09

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