Supported by National Science Foundation Grant BNS 73-02078, the Alfred P. Sloan Foundation, National Institutes of Health Grant NS 12422 and Research Career Development Award NS 00224 to R. W. Olsen; P. C. Van Ness was an NSF undergraduate research student. We thank Drs. W. B. Levy, M. K. Ticku, and B. Meiners for helpful discussions, and P. Krogsgaard-Larsen and G. A. R. Johnston for the generous gift of many GABA analogues.
GAMMA-AMINOBUTYRIC ACID BINDING IN MAMMALIAN BRAIN: RECEPTOR-LIKE SPECIFICITY OF SODIUM-INDEPENDENT SITES
Version of Record online: 5 OCT 2006
Journal of Neurochemistry
Volume 31, Issue 4, pages 933–938, October 1978
How to Cite
Greenlee, D. V., Van Ness, P. C. and Olsen, R. W. (1978), GAMMA-AMINOBUTYRIC ACID BINDING IN MAMMALIAN BRAIN: RECEPTOR-LIKE SPECIFICITY OF SODIUM-INDEPENDENT SITES. Journal of Neurochemistry, 31: 933–938. doi: 10.1111/j.1471-4159.1978.tb00130.x
- Issue online: 5 OCT 2006
- Version of Record online: 5 OCT 2006
- (Received 13 December 1977, Accepted 24 April 1978)
The binding of radioactive gamma-aminobutyric acid to particulate fractions of mammalian brain was measured by a centrifugation assay, using repeatedly washed and frozen and thawed membranes and sodium-free assay conditions. Studies of over 30 structural analogues indicated an excellent correlation between inhibition of gamma-aminobutyric acid binding and activity as agonists or antagonists on gamma-aminobutyric acid synapses as reported in the neurophysiology literature. In particular, binding was inhibited by low concentrations of the gamma-aminobutyric acid receptor-specific drugs muscimol, homotaurine, and isoguvacine, but very poorly by analogues such as 2,4-diaminobutyric acid and nipecotic acid which specifically inhibit gamma-aminobutyric acid transport but are inactive on synaptic receptors. Binding was inhibited by the synaptic antagonist bicuculline but not by picro-toxinin. Thus, these binding sites show the chemical specificity required of physiological receptors for the neurotransmitter gamma-aminobutyric acid.