Autoradiographic localization of gamma-aminobutyric acid receptors in the rat central nervous system by using [3H]muscimol.
Muscimol, a structural analogue and potent agonist of gamma-aminobutyric acid (GABA), was used in its tritiated form for the autoradiographic localization of GABA receptors in the rat central nervous system. [(3)H]Muscimol ([(3)H]M) was incubated with brain slices or was injected intracortically or into intraocular brain transplants. As indicated by [(3)H]M binding and autoradiographic silver grains, GABA receptors display a laminar distribution over the cerebellar cortex, cerebral cortex, and hippocampus (in order of decreasing quantity); and a nonlaminar distribution in the caudate nucleus and substantia nigra. [(3)H]M binding was not affected by brief prior treatment of brain slices with (-)nipecotic acid or guvacine, two potent inhibitors of GABA uptake, indicating receptor binding specificity. Systemic administration of unlabeled muscimol interferred with binding of [(3)H]M binding subsequently administered in vitro, indicating that muscimol or a metabolite of it traverses the blood/brain barrier and binds to receptor sites, possibly in a manner competitive with [(3)H]M. [(3)H]M binding was greatest in the cerebellum. Quantitative analyses of the distribution of autoradiographic silver grains in the cerebellar cortex and dentate nucleus showed a general distribution of GABA receptors in the neuropil: molecular layer > granular layer > cerebellar nuclei > white matter. The highest binding of [(3)H]M occurred on the Purkinje cell somatic surface, in the basket axon formation surrounding the cell body and its axon initial segment, and somewhat less on basket and stellate cell somata. Neuroglial cells of the cortex have no [(3)H]M binding capacity; some glial cells in the cerebellar nuclei do. The role of glial cells in GABA uptake, metabolism, and GABA-receptor-mediated mechanisms remains to be clarified. The distribution of GABA receptors as indicated by [(3)H]M binding differs from the distribution of [(3)H]GABA uptake and GABA synthesizing and degradative sites.
D000613:Aminobutyrates / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D002525:Cerebellar Cortex / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D009183:Mycotoxins / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D011689:Purkinje Cells / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D007555:Isoxazoles; D009183:Mycotoxins; D009557:Nipecotic Acids; D011955:Receptors, Drug; D005680:gamma-Aminobutyric Acid
Brain Res. 1977 Mar 18;124(1):185-90
191147
Fortschr Chem Org Naturst. 1969;27:261-321
4907242
Psychopharmacologia. 1971;22(3):230-3
5167208
Brain Res. 1971 Sep 10;32(1):69-96
4398801
Acta Physiol Scand Suppl. 1970;348:1-112
4320063
J Neurochem. 1976 May;26(5):1029-32
1271062
Brain Res. 1974 Aug 23;76(3):377-91
4854839
J Neurochem. 1973 Feb;20(2):319-24
4698282
Acta Chem Scand. 1972;26(3):1298-9
5079744
Physiol Chem Phys. 1975;7(4):381-4
1187822
Nature. 1975 Dec 18;258(5536):627-8
1207742
J Neurochem. 1975 Dec;25(6):803-9
1206399
J Neurochem. 1975 Dec;25(6):797-802
1206398
Brain Res. 1970 Sep 16;22(3):391-6
5505543