The development of a radio receptor assay for gamma aminobutyric acid and its application in the study of neurological diseases.

Abstract

The methodology of a radioreceptor assay for the inhibitory neurotransmitter, GABA, is described in detail. This is a filtration assay which utilises the binding of tritiated muscimol to synaptic membranes prepared from pig brain. The assay is modified from previously described techniques, and these modifications, along with the technical difficulties encountered in the development of the assay, are described in detail. In its final form the assay provides an accurate and reproducible technique which may be used to measure GABA concentrations in extracellular fluids such as cerebrospinal fluid and plasma. Studies are described in which the assay has been used for this purpose in studying patients with neurological disease. CSF and blood were obtained from patients undergoing diagnostic lumbar puncture, and the methods of collection and storage of CSF were standardised in order to avoid artefactual changes in GABA concentrations. These methods are described in detail. Thirty-four patients who were subsequently found to be free from structural neurological disease were used as a control population, and CSF GABA concentrations in these patients were analysed according to their age and sex. In patients with neurological disease attention was focussed primarily on those with extrapyramidal disorders, and low CSF GABA concentrations were found in patients with Huntington's disease. Patients with Alzheimer's disease also had significantly lower CSF GABA than controls. The clinical value of CSF GABA estimation in these disorders and in the other diseases studied is considered. It is concluded from these studies that CSF GABA estimation is unlikely to become a useful diagnostic tool in clinical practice, but may in the future be a useful guide to those neurological disorders in which drugs which enhance GABA neurotransmission may be of benefit