Super-high-affinity binding site for [3H]diazepam in the presence of Co2+, Ni2+, Cu2+, or Zn2+.
Chloride salts of Li+, Na+, K+, Mg2+, Ca2+, Cr3+, Mn2+, Fe2+, and Fe3+ had no effect on [3H]diazepam binding. Chloride salts of Co2+, Ni2+, Cu2+, and Zn2+ increased [3H]diazepam binding by 34 to 68% in a concentration-dependent fashion. Since these divalent cations potentiated the GABA-enhanced [3H]diazepam binding and the effect of each divalent cation was nearly additive with GABA, these cations probably act at a site different from the GABA recognition site in the benzodiazepine-receptor complex. Scatchard plots of [3H]diazepam binding without an effective divalent cation showed a single class of binding, with a Kd value of 5.3 nM. In the presence of 1 mM Co2+, Ni2+, Cu2+, or Zn2+, two distinct binding sites were evident with apparent Kd values of 1.0 nM and 5.7 nM. The higher-affinity binding was not detected in the absence of an effective divalent cation and is probably a novel, super-high-affinity binding site.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002412:Cations; D003035:Cobalt / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D003975:Diazepam / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009532:Nickel / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D013570:Synaptic Membranes / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D002412:Cations; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D003035:Cobalt; D003300:Copper; D009532:Nickel; D015032:Zinc; D003975:Diazepam