Regional distribution and kinetics of three sites on the GABAA receptor: lack of effect of portacaval shunting.

Article date: 1992/3/1

PubMed ID: 1312540

Journal name: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (ISSN: 0271-678X)


The regional distribution of binding sites on the GABAA receptor and their kinetic parameters were measured by quantitative autoradiography in brains from normal rats and rats with a portacaval shunt, a model of portal systemic encephalopathy in which GABA neurotransmission may be altered. The ligands used were [3H]flunitrazepam (a benzodiazepine-site agonist), [3H]-Ro15-1788 (a benzodiazepine-site antagonist), [3H]muscimol (a GABA-site agonist), and [35S]t-butylbicyclophosphorothionate (35S-TBPS, a convulsant that binds to a site near the chloride channel). Some brains were analyzed by computerized image analysis and three-dimensional reconstruction. The regional distribution of binding of the benzodiazepines was very similar, but the patterns obtained with [3H]muscimol and [35S]TBPS were different in many areas, suggesting a heterogeneous distribution of several subtypes of the GABAA receptor. The kinetic parameters were determined in brain regions for [3H]flunitrazepam, [3H]Ro15-1788, and [3H]muscimol. For each ligand, the Kd showed a significant heterogeneity among brain regions (at least threefold), contrary to conclusions drawn from earlier studies. In portacaval shunted rats, binding of all four ligands was essentially unchanged from that in control rats, indicating that, if there was an abnormality in GABA neurotransmission during portal systemic shunting, it was not reflected by altered binding to the main sites on the GABAA receptor.

This document is available from: http://directlinks.cc/files/muscimol/1312540.pdf

Author List: Mans A M, Kukulka K M, McAvoy K J, Rokosz N C

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

Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Receptors, GABA-A; Muscimol; Flumazenil; Flunitrazepam; tert-butylbicyclophosphorothionate;

Mesh terms: Animals; Autoradiography; Binding Sites; Brain/metabolism; Bridged Bicyclo Compounds/metabolism; Bridged Bicyclo Compounds, Heterocyclic; Flumazenil/metabolism; Flunitrazepam/metabolism; Image Processing, Computer-Assisted; Kinetics; Male; Muscimol/metabolism; Portacaval Shunt, Surgical; Rats; Rats, Inbred Strains; Receptors, GABA-A/metabolism; Tissue Distribution;

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