Glycine receptors in the human substantia nigra as defined by [3H]strychnine binding.

Abstract

Specific [3H]strychnine binding was used to identify the glycine receptor macromolecular complex in human spinal cord, substantia nigra, inferior olivary nucleus, and cerebral cortex. In material from control patients a high-affinity KD (3--8 nM) was observed in the spinal cord and the substantia nigra, both the pars compacta and the pars reticulata. This is very similar to the values observed in the rat and bovine spinal cord (8 and 3 nM, respectively) and rat substantia nigra (12 nM). In the human brain the distribution of [3H]strychnine binding (at 10 nM) was: spinal cord = substantia nigra, pars compacta greater than substantia nigra, pars reticulata = inferior olivary nucleus greater than cerebral cortex. The binding capacity (Bmax) of the rat brain (substantia nigra or spinal cord) was approximately 10-fold that of the human brain. [3H]Strychnine binding was significantly decreased in the substantia nigra from Parkinson's disease patients, both in the pars compacta (67% of control) and the pars reticulata (50% of control), but not in the inferior olivary nucleus. The results were reproduced in preliminary experiment in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. In the substantia nigra from patients who died with Huntington's disease, [3H]strychnine binding tended to be high (150% of control, NS) in both the pars compacta and the reticulata. [3H]Strychnine binding was unaltered in the substantia nigra of patients with senile dementia. Together with previous neurophysiological and neuropharmacological findings, those results support the hypothesis of glycine receptors occurring on dopamine cell bodies and/or dendrites in the substantia nigra.