EXPRESSION OF METABOTROPIC-GLUTAMATE-RECEPTOR-1 ISOFORMS IN THE SUBSTANTIA-NIGRA PARS COMPACTA OF THE RAT

Metabotropic glutamate receptors, which are linked via G-proteins to s econd messenger systems, have been implicated in the physiological reg ulation of dopaminergic neurons of the substantia nigra pars compacta as well as in neurodegeneration. Of the eight known metabotropic gluta mate receptors, metabotropic glutamate receptor 1 is the most abundant subtype in the substantia nigra pars compacta. Metabotropic glutamate receptor 1 is alternatively spliced at the carboxy terminal region to yield five variants: 1a, 1b, 1c, 1d and a form recently identified in human brain, 1g. We used an antibody recognizing metabotropic glutama te receptor 1, and another recognizing the splice form 1a only, to stu dy the localization of these receptors in dopaminergic neurons identif ied by the presence of tyrosine hydroxylase. Metabotropic glutamate re ceptor immunoreactivity was present within the somata, axons, and dend rites of substantia nigra pars compacta neurons. The 1a splice form sp ecific antibody, however, did not label these cells, suggesting that t hey express a metabotropic glutamate receptor 1 splice form different from 1a. In situ hybridization with splice form-specific oligonucleoti de probes was used to determine which of the other known metabotropic glutamate receptor 1 splice forms might be present in the substantia n igra pars compacta. Each probe produced a very distinct labelling patt ern in the rat brain with the exception of the 1g specific probe which produced only background signal. Substantia nigra pars compacta neuro ns were most intensely labelled by the metabotropic glutamate receptor 1d splice form specific probe. Metabotropic glutamate receptor 1a was expressed weakly whereas there was no detectable 1b, c, or g signal i n the substantia nigra pars compacta. These data demonstrate thar meta botropic glutamate receptor 1 protein is present within the perikarya and processes of dopaminergic neurons in the substantia nigra pars com pacta. The majority of this protein is not the la splice form. which i s abundant in other brain regions, and may be the 1d isoform. Since sp licing alters the carboxy terminus of the receptor, it is likely to af fect the interaction of the receptor with intracellular signalling sys tems. (C) 1998 IBRO. Published by Elsevier Science Ltd.