Ethylenediamine and GABA Potentiation of [3H]Diazepam Binding to Benzodiazepine Receptors in Rat Cerebral Cortex

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Abstract
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 × 10−5M), although this potentiation was susceptible to a low dose (6 μM) 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 × 10‐3M 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.