Positive cooperativity in high affinity binding sites for gamma-hydroxybutyric acid in rat brain.

High affinity binding sites for gamma-hydroxybutyrate have recently been shown to exist on crude membranes of rat brain. These sites exhibit a dissociation constant of 95 nM and a capacity of 557 fentomoles per mg protein. However, after more extensive washing of the crude membrane fraction and performing binding experiments at a lower concentration of radioactive GHB (below 20 nM), the existence of another binding site for GHB with a higher affinity than previously described was discovered. The data concerning this binding site are in favour of positive cooperative binding characteristics. This binding site may play a role in the mediation of the multiple physiological and pharmacological effects of GHB in the rat CNS and its presence provides additional evidence in favour of a neuromodulator or neurotransmitter role of GHB.