Interaction of caffeine with the GABAA receptor complex: alterations in receptor function but not ligand binding.

Article date: 1989/12/5

PubMed ID: 2482188

Journal name: European journal of pharmacology (ISSN: 0014-2999)


Behavioral and neurochemical evidence indicates interactions between caffeine and other adenosine receptor ligands and the gamma-aminobutyric acid (GABA)-benzodiazepine system. To assess the effects of caffeine on binding and function at the GABAA receptor, we studied the effects of behaviorally-active doses of caffeine on benzodiazepine and Cl- channel binding and on overall function of the GABAA receptor as measured by Cl- uptake. There was no effect of caffeine on benzodiazepine receptor binding in cortical synaptosomal membranes at concentrations of 1-100 microM. No effects on benzodiazepine binding were found ex vivo in mice treated with caffeine, 20 and 40 mg/kg. At the putative Cl- channel site labeled by t-butylbicyclophosphorothionate (TBPS), binding was unchanged in vitro after caffeine treatment (1 and 10 microM) in washed and unwashed membranes. However, in ex vivo studies caffeine (20 and 40 mg/kg) increased numbers of TBPS sites in unwashed but not washed membranes. Muscimol-stimulated Cl- uptake into cortical synaptoneurosomes was decreased in mice treated with caffeine, 20 and 40 mg/kg. Similar results were observed in in vitro preparations treated with 50 microM but not 100 microM caffeine. These results indicate that caffeine administration significantly alters the Cl- transport function of the GABAA receptor complex.

This document is available from: http://directlinks.cc/files/muscimol/2482188.pdf

Author List: Lopez F, Miller L G, Greenblatt D J, Kaplan G B, Shader R I

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Chlorides; Ion Channels; Ligands; Receptors, GABA-A; Sulfur Radioisotopes; Muscimol; Caffeine; tert-butylbicyclophosphorothionate;

Mesh terms: Animals; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Caffeine/pharmacology; Cerebral Cortex/drug effects; Chlorides/metabolism; In Vitro Techniques; Ion Channels/drug effects; Kinetics; Ligands; Male; Mice; Muscimol/pharmacology; Receptors, GABA-A/drug effects; Sulfur Radioisotopes; Synaptosomes/drug effects;

2482188.txt · Last modified: 2018/11/22 21:16 (external edit)