Regional distribution of low-affinity GABA receptors coupled to benzodiazepine receptor subtypes in rat brain: an autoradiographic evaluation.
Quantitative autoradiography of rat brain coronal sections show that maximum enhancement (more than 80%) of [3H]flunitrazepam binding by GABA occurs in brain regions particularly rich in type I benzodiazepine receptors (inferior colliculus, medium raphe, central gray and substantia nigra); conversely, brain areas where type II predominates show the lowest enhancement by GABA (about 50%). These results, suggesting that the coupling of GABA receptors with type I sites is more efficient than that with type II sites, are at variance with those reported on GABA-benzodiazepine receptors expressed in transfected cells, where the greater GABA potentiation of benzodiazepine binding is due to a subtype of the type II site containing the alpha 3 subunit of the GABAA receptor. One possible explanation of these discrepancies is that the type II receptors found in type I-enriched tissues (inferior colliculus, median raphe, central gray and substantia nigra) are associated with the alpha 3-subunit, while the type II sites present in limbic and cortical regions represent a subpopulation carrying the alpha 2-subunit of the GABAA receptor, with lower GABA potentiation.
Mennini
T
T
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Gobbi
M
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism; D066298:In Vitro Techniques; D007245:Inferior Colliculi / Q000378:metabolism; D008297:Male; D010487:Periaqueductal Gray / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism
D011963:Receptors, GABA-A; D005445:Flunitrazepam