Taurine allosterically modulates flunitrazepam binding to synaptic membranes
| Autor: | C. L. Miller, M. R. Quinn |
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| Rok vydání: | 1992 |
| Předmět: |
Agonist
Male medicine.medical_specialty Taurine medicine.drug_class Allosteric regulation Synaptic Membranes Flunitrazepam Biology In Vitro Techniques Bicuculline Partial agonist Binding Competitive Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Internal medicine medicine Animals gamma-Aminobutyric Acid Synaptosome Cerebral Cortex GABAA receptor Temperature Rats Endocrinology chemistry medicine.drug |
| Zdroj: | Journal of neuroscience research. 33(1) |
| ISSN: | 0360-4012 |
| Popis: | Taurine is hypothesized to exert its inhibitory neuromodulatory effects, in part, by interaction with the GABAA receptor. Although taurine displaces GABA agonist binding to synaptic membranes, its allosteric effects on the benzodiazepine recognition site of the GABAA receptor complex is unsettled. We determined the effects of taurine on [3H]flunitrazepam (Flu) binding to well-washed, frozen-thawed synaptic membranes prepared from rat cortex. Comparative binding studies were conducted at 37°C and on ice (0–4°C). At 37°C taurine increased Flu binding in a concentration dependent way by interaction with a bicuclulline sensitive site, similar to GABA. Taurine increased Flu binding by causing a decrease in KD. The maximal effectiveness of taurine on Flu binding could not be increased further by addition of GABA. In contrast, the maximal stimulation of Flu binding by GABA was decreased by addition of taurine to the level attained by taurine alone. These mixed agonist/antagonist effects of taurine are pharmacologically specific and qualify taurine as a partial GABA agonist in this type of allosteric interaction. However, taurine causes opposite effects on Flu binding when measured at 0–4°C: taurine interacts with a bicuculline insensitive site to inhibit Flu binding by increasing the KD. Taurine inhibition of Flu binding is not overcome by increasing concentrations of GABA. Although the mechanism of taurine inhibition of Flu binding at 0–4°C is unclear, it may be an indirect effect of taurine interaction with membrane phospholipids. More importantly, the results of these studies suggest that taurine, at physiologically relevant concentrations (EC50 = 100 μM) and temperature (37°C), may function as a partial GABA agonist in stimulating Flu binding to synaptic membranes. © 1992 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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