Presence of a low molecular weight endogenous inhibitor on 3H-muscimol binding in synaptic membranes.

The specific binding of 3H-muscimol to synaptic membrane preparations obtained from the rate brain has been though to reflect the association of gamma-aminobutyric acid (GABA), a potential candidate as an inhibitory neurotransmitter in the mammalian central nervous system (CNS), with its synaptic receptors. Treatment of synaptic membranes with Triton X-100 significantly increases the specific binding of 3H-muscimol. Several reports also indicate the presence of endogenous substances, such as GABA, acidic protein and phosphatidylethanolamine, which inhibit Na-independent binding of 3H-GABA in the synaptic membranous fractions from the rat brain. We report here that in the supernatant obtained from Triton-treated synaptic membranes there exists a new type of endogenous inhibitor of 3H-muscimol binding which is apparently different from the inhibitory substances described previously. The new inhibitor has a low molecular weight (MW) and probably originated from neurones rather than glial cells. We have termed this endogenous inhibitor the GABA receptor binding inhibitory factor (GRIF).