title: Aging related alterations in GABAA receptor subunit mRNA levels in Fischer rats.
abstract: The influence of aging on the binding of ligands to picrotoxin binding sites as well as steady state levels of mRNA for various alpha subunits of gamma-aminobutyric acid (GABA) receptor complex was investigated in male Fischer F-344 rats. In aged rats, the binding of [35S]t-butyl-bicyclophosphorothionate (TBPS) was significantly reduced. This decrease in TBPS binding derived from a reduced density of binding sites, rather than from affinity changes, in both cerebral cortex and cerebellum. In aged rats, alpha 1 mRNA level decreased approximately 70% between age 6 months and 24 months in the cerebral cortex (P less than 0.005). In contrast, alpha 1 mRNA remained unchanged in the cerebellum of old rats. The association of a decrease in picrotoxin binding sites in the cerebral cortex with a decline in alpha 1 mRNA level in the cerebral cortex and in alpha 2 mRNA level in the cerebellum is indicated. alpha 6 mRNA level increased with age in the cerebellum. These findings indicate a selective age related modulation in the stoichiometry of GABAA receptor in aging.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
authors.forename: M C
authors.initials: MC
authors.lastname: Mhatre
authors.forename: M K
authors.initials: MK
authors.lastname: Ticku
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C037480:picrotoxinin receptor; C037476:tert-butylbicyclophosphorothionate