Reduction of GABAB receptor binding induced by climbing fiber degeneration in the rat cerebellum.
When the rat cerebellar climbing fibers degenerated, as induced by lesioning the inferior olive with 3-acetylpyridine (3-AP), GABAB receptor binding determined with 3H-(+/-)baclofen was reduced in the cerebellum but not in the cerebral cortex of rats. Computer analysis of saturation data revealed two components of the binding sites, and indicated that decrease of the binding in the cerebellum was due to reduction in receptor density, mainly of the high-affinity sites, the Bmax of which was reduced to one-third that in the control animals. In vitro treatment with 3-AP, of the membranes prepared from either the cerebellum or the cerebral cortex, induced no alteration in the binding sites, thereby indicating that the alteration of GABAB sites induced by in vivo treatment with 3-AP is not due to a direct action of 3-AP on the receptor. GABAA and benzodiazepine receptor binding labelled with 3H-muscimol and 3H-diazepam, respectively, in both of brain regions was not affected by destruction of the inferior olive. These results provide evidence that some of the GABAB sites but neither GABAA nor benzodiazepine receptors in the cerebellum are located at the climbing fiber terminals.
Kato
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Fukuda
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D000818:Animals; D001418:Baclofen / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D003975:Diazepam / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000378:metabolism; D009847:Olivary Nucleus / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism* / Q000502:physiology; D013570:Synaptic Membranes / Q000378:metabolism*
D011725:Pyridines; D011963:Receptors, GABA-A; C010835:3-acetylpyridine; D009118:Muscimol; D001418:Baclofen; D003975:Diazepam