Two distinct solubilized benzodiazepine receptors: differential modulation by ions.
The modulation of solubilized type 1 and type 2 benzodiazepine receptors from cow brain by gamma-aminobutyric acid (GABA), divalent cations, and anions has been evaluated. GABA stimulates [3H] flunitrazepam binding of both receptor subtypes, whereas divalent cations and anions selectively stimulate solubilized type 2 receptors. Of numerous anions examined, only chloride, bromide, and iodide enhance [3H] flunitrazepam binding. Chloride and bromide increase mainly receptor affinity for [3H]flunitrazepam, whereas iodide largely influences Bmax values. Divalent cations also stimulate soluble type 2 receptors. Calcium, zinc, manganese, barium, and magnesium have similar potencies in enhancing [3H]flunitrazepam binding, whereas copper and nickel are about 4 to 5 times more potent. The 2- to 3-fold increase in type 2 receptor binding by divalent cations involves change in numbers of binding sites. Effects of combinations of GABA, calcium, and chloride suggest that they may exert their modulating effects on type 2 receptors through different mechanisms. GABA, calcium, and chloride also protect [3H]flunitrazepam binding from heat inactivation, indicating a close link in the native state between the GABA, ions, and the benzodiazepine recognition sites. Since physiologic concentrations of calcium and chloride influence type 2 receptors, these ions may be involved in those pharmacologic effects of benzodiazepines mediated by type 2 sites.
D000818:Animals; D000838:Anions / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002413:Cations, Divalent / Q000502:physiology; D002417:Cattle; D002712:Chlorides / Q000494:pharmacology; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D006358:Hot Temperature; D010084:Oxidation-Reduction / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D011963:Receptors, GABA-A; D012995:Solubility; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000838:Anions; D002413:Cations, Divalent; D002712:Chlorides; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam