Please use this identifier to cite or link to this item:
|Title:||Characterisation of particulate and soluble mammalian alpha2-adrenoceptors.|
|Abstract:||Particulate alpha2-adrenoceptors of several mammalian tissues have been quantified and characterized using radioligand binding techniques and selective antagonist ligands, 3H-yohimbine and 3H-rauwolscine. The results showed that both ligands specifically labelled an identical population of alpha2-receptors in all the tissues investigated. However, significant differences in drug affinities and relative drug potencies were observed between tissues within a given species or between species. The differences in pharmacological behaviour of the alpha2-receptors, particularly with respect to the relative potencies of the subtype selective antagonists, provided evidence for a possible receptor heterogeneity. The effects of guanine nucleotides, cations and temperature on agonist/antagonist interactions with alpha2-receptors labelled by selective antagonist ligands have also been examined. The differential qualitative and quantitative influences of these modulators provided evidence for basic molecular differences in agonist and antagonist interactions with alpha2-receptors. The influence of endogenous or retained exogenous agonist on 3H-yohimbine binding has further been evaluated in detail. The results revealed a 'pseudo non-competitive' agonist interference of 3H-antagonist binding reversible under the influence of guanine nucleotides and Na+, and suggested the need for considering possible endogenous agonist influence when interpreting 3H-antagonist binding data under certain assay conditions. Alpha2-receptors of the human platelet, rat and rabbit kidneys have been successfully solubilized using the glycoside detergent digitonin, and assayed with a polyethylene glycol precipitation-filtration method. The solubilized alpha2-receptors labelled by 3H-rauwolscine generally exhibited reduced drug affinities but retained the pharmacological properties of the respective particulate receptors. The results discounted differences in membrane constraint/environment as a likely cause for pharmacological differences between alpha2-receptors and provided further evidence for the possible heterogeneity of alpha2-receptors.|
|Rights:||Copyright © the author. All rights reserved.|
|Appears in Collections:||Theses, College of Medicine, Biological Sciences and Psychology|
Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.