EVIDENCE FOR THE STABILISATION OF THE HIGH-AFFINITY STATE OF β-ADRENOCEPTORS BY AN ENDOGENOUS FACTOR IN RAT BRAIN
| Autor: | Roland Zini, Didier Morin, Jean-Paul Tillement, Vincent Garnier |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
Agonist medicine.medical_specialty GTP' medicine.drug_class G protein Endogeny Propanolamines GTP-Binding Proteins Chaps Internal medicine Receptors Adrenergic beta medicine Animals Rats Wistar Receptor Pharmacology Guanylyl Imidodiphosphate Chemistry Isoproterenol Temperature Antagonist Brain Cholic Acids Rats Membrane Endocrinology Biophysics Synaptosomes |
| Zdroj: | Pharmacological Research. 37:365-373 |
| ISSN: | 1043-6618 |
| DOI: | 10.1006/phrs.1998.0305 |
| Popis: | Inhibition of binding of the labelled antagonist (-)[3H]CGP 12177 by the full agonist (-)isoproterenol results in shallow competition curves, characteristic of the presence of both high- and low-affinity states of beta-adrenoceptors (betaAR). When in excess, the GTP analog 5'-guanylylimidodiphosphate (GppNHp) is expected to convert all receptors in the high-affinity state to the low-affinity state. However, in the rat cortex and cerebellum synaptosomes, a proportion of the betaAR in the high-affinity state was GppNHp-insensitive. This apparent GppNHp-insensitivity decreased with decreasing temperature of incubation. Moreover, it was totally abolished by the gentle treatment of membranes with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). We propose that a protein factor interacts with the betaAR/Gs protein complex and that it induces the GppNHp-insensitivity. This factor would be released by CHAPS in a functional form because it may regenerate the GppNHp-insensitivity after concentration and reconstitution with CHAPS-treated membranes. It is likely that the factor acts as a stabiliser of betaAR in the high-affinity state. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect