TY - JOUR
T1 - Two distinct solubilized benzodiazepine receptors
T2 - Differential modulation by ions
AU - Lo, M. M.S.
AU - Snyder, S. H.
PY - 1983
Y1 - 1983
N2 - The modulation of solubilized type 1 and type 2 benzodiazepine receptors from cow brain by γ-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 B(max) 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 or 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.
AB - The modulation of solubilized type 1 and type 2 benzodiazepine receptors from cow brain by γ-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 B(max) 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 or 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.
UR - http://www.scopus.com/inward/record.url?scp=0021072252&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021072252&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.03-11-02270.1983
DO - 10.1523/jneurosci.03-11-02270.1983
M3 - Article
C2 - 6313875
AN - SCOPUS:0021072252
VL - 3
SP - 2270
EP - 2279
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 11
ER -