Differential ontogenesis of type I and II benzodiazepine receptors in mouse cerebellum.
The ontogeny of type I and type II benzodiazepine binding sites was studied in mouse cerebellum by displacement of [3H]flunitrazepam binding by zolpidem, a ligand specific for the type I sites. Type I binding sites predominate throughout development and in the adult while type II sites account for 25% of total cerebellar benzodiazepine binding sites at birth and, during development, decrease to 10% or less in the adult. On a per cerebellum basis type II sites increase during the first postnatal week and then remain at a steady level while type I sites increase until adulthood. These results may indicate a specific localization of the type II sites (and of the corresponding alpha-protein subunits in the GABA/benzodiazepine receptor complex) in structures already present at birth and developing during a short early postnatal period. The affinity of zolpidem for its high affinity (type I) binding sites increases during cerebellar ontogeny, this increase possibly indicates an epigenetic (post-translational) 'maturation' process of the corresponding receptor molecule. Hill numbers indicate the existence of an additional binding site heterogeneity greater during development but still present in the adult; probably this is to be related to the simultaneous presence of different 'maturation' stages during development and with a certain variety of the final products.
Bacon
E
E
Centre de Neurochimie du CNRS et U44 INSERM, Strasbourg, France.
de Barry
J
J
Gombos
G
G
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism*; D005445:Flunitrazepam / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D011724:Pyridazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism*; D000077334:Zolpidem
D011724:Pyridazines; D011725:Pyridines; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C021604:CL 218872; D000077334:Zolpidem