Antibodies were raised against two distinct extracellular sequences of the rat mGIuR1 metabotropic glutamate receptor expressed as bacterial fusion proteins. Both antibodies specifically reacted with mGIuR1 in the rat cerebellum and inhibited the mGIuR1 activity as assessed by the analysis of glutamate-stimulated inositol phosphate formation in CHO cells expressing mGIuR1. Using these antibodies, we examined the role of mGIuR1 in the induction of long-term depression in cultured Purkinje cells. In voltage-clamped Purkinje cells, current induced by iontophoretically applied glutamate was persistently depressed by depolarization of the Purkinje cells in conjunction with the glutamate application. The mGIuR1 antibodies completely blocked the depression of glutamate-induced current. The results indicate that activation of mGIuR1 is necessary for the induction of cerebellar long-term depression and that these mGIuR1 antibodies can be used as selective antagonists.
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