Calcium alters divalent cation modulation of brain benzodiazepine receptors.
Nickel (Ni+2) ions enhance the binding of 3H-diazepam, but decrease the binding of 3H-propyl beta-carboline-3-carboxylate to benzodiazepine receptors in mouse brain. Our experiments were performed to determine the locus for this action. In both control and Ca+2-depleted membranes, Ca+2 blocked the stimulatory effect of Ni+2 on 3H-diazepam binding in a concentration-dependent manner. In Ca+2-depleted membranes, physiological Ca+2 concentrations blocked this effect of Ni+2. In control membranes, Ca+2 did not reverse Ni+2 inhibition of 3H-propyl beta-carboline-3-carboxylate binding, but was effective at physiological concentrations in reversing Ni+2 inhibition in Ca+2-depleted membranes. The effects of Cd+2 ions on 3H-diazepam binding were similar to Ni+2 and were also reversed by Ca+2. The effects of Ni+2 were blocked by La+3 ions but not by Mg+2 ions, and were not due to interactions with the GABA receptor or Cl- ionophore. These data suggest that a Ca+2 binding site is associated with the brain benzodiazepine receptor.
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009532:Nickel / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002413:Cations, Divalent; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D009532:Nickel; D002118:Calcium