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Title: Studies on the pharmacology of rat adipocyte beta-adrenoceptors.
Authors: Bojanic, Dejan.
First Published: 1984
Award date: 1984
Abstract: The pharmacology of the rat adipocyte beta-adrenoceptor has been examined using radioligand binding techniques as well as analysis of biochemical and functional effector responses. The ligand binding properties of beta-adrenoceptors on isolated adipocyte membranes have been compared to those in rat lung and whole fat pad membranes. This study demonstrated that binding sites could be identified on adipocytes which had all the characteristics expected of beta-adrenoceptors. Furthermore, inhibition of binding by agents selective for beta, or beta2 adrenoceptors indicated that the receptor subtype present on adipocytes was predominantly beta1 whereas lung and whole fat pad membranes contained mainly beta2 Adrenoceptors. The characteristics of the beta-adrenoceptor mediating lipolysis have also been examined. Evidence is presented which showed that inhibition of lipolysis stimulated through beta-adrenoceptors was inhibited by selective beta-adrenoceptor antagonists with a lower potency than that expected at beta1 or beta2 adrenoceptors. This suggested that an atypical beta-adrenoceptor was responsible for mediating the lipolytic response. The apparently atypical beta-adrenoceptor has been further investigated by analysis of cAMP-accumulation in whole cells and adenylate cyclase activity in membranes. These studies confirmed the results from lipolysis studies where it was again shown that antagonists had low potencies. In addition, the stereospecificity displayed by antagonist isomers was lower to that expected at typical beta-adrenoceptors. In order to investigate whether typical beta1 and atypical beta-adrenoceptors could be separated, an irreversible beta-adrenoceptor antagonist has been used to selectively inhibit typical beta-adrenoceptors. The results demonstrated that whereas beta1 binding sites could be irreversibly blocked, the beta-adrenoceptor-stimulated adenylate cyclase activity was unaffected. This further suggested that the receptors identified by binding studies are not the same as those mediating the lipolytic response to catecholamines.
Type: Thesis
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, College of Medicine, Biological Sciences and Psychology
Leicester Theses

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