Evidence for a Reduction of Coupling between GABAA Receptor Agonist and Ionophore Binding Sites by Inorganic Phosphate |
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| Authors: | Saku?T.?Sinkkonen,Holger?Rabe,Hartmut?Lüddens,Esa?R.?Korpi author-information" > author-information__contact u-icon-before" > mailto:esa.korpi@helsinki.fi" title=" esa.korpi@helsinki.fi" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author |
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| Affiliation: | (1) Institute of Biomedicine, Pharmacology, University of Helsinki, P.O.Box 63, Helsinki, FI-00014, Finland;(2) Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland;(3) Clinical Research Group, Department of Psychiatry, University of Mainz, Mainz, Germany |
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| Abstract: | [35S]TBPS binding to the GABAA receptor ionophore binding site is anion dependent. Using autoradiography on rat brain sections, we show that permeabilities of anions through the receptor channel correlate with their efficiencies to promote basal [35S]TBPS binding. Phosphate made an exception as it induced more binding than expected from its permeability. Well-permeable anions (chloride, nitrate, formate) allowed [35S]TBPS binding to be effectively displaced by 1 mM GABA, whereas low-permeable anions (acetate, phosphate, propionate) markedly prevented this GABA effect, especially in the thalamus, the transition from the high to the low GABA effect being between formate and acetate. In the presence of phosphate, GABA enhanced [3H]flunitrazepam binding to benzodiazepine site of recombinant α1β2γ2 receptors with the same efficacy but lower potency as compared to the presence of chloride, whereas [35S]TBPS binding was abnormally modulated by GABA. These results suggest that inorganic phosphate affects coupling between agonist and ionophore sites in GABAA receptors. Special issue dedicated to Simo S. Oja |
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| Keywords: | Binding sites brain regions GABAA receptor inorganic phosphate recombinant receptors |
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