Ethylenediamine and GABA potentiation of [3H]diazepam binding to benzodiazepine receptors in rat cerebral cortex.
Specific binding of [3H]diazepam at a free concentration of 2 nM was found to be maximally potentiated by 117% in Tris-HCl buffer and 160% in Tris-citrate buffer by ethylenediamine (EDA), but only at relatively high concentrations of EDA (ED50 = 5 X 10(-5) M), although this potentiation was susceptible to a low dose (6 microM) of bicuculline. Dose-response curves show that EDA differs from GABA with respect to both potency and efficacy. In additivity experiments no evidence was found that EDA could act as a partial agonist at GABA receptors, and it was concluded that EDA and GABA apparently do not potentiate [3H]diazepam binding by acting on the same receptor. Scatchard analysis lends support to this hypothesis, indicating that the potentiation of [3H]diazepam binding by 3.16 X 10(-3) M EDA is due to an increase in receptor number (from 930 to 1170 fmol/mg protein) and not receptor affinity (remaining constant about 20 nM). Subsequent studies showed the potentiation to be reversible. It is concluded that EDA can act on the GABA-benzodiazepine receptor ionophore complex but that this is probably not a direct action on the GABA receptor. It is suggested that EDA can be used to differentiate GABA receptors linked to benzodiazepine receptors from those not so linked.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002021:Buffers; D002540:Cerebral Cortex / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005029:Ethylenediamines / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002021:Buffers; D005029:Ethylenediamines; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D001640:Bicuculline