title: Inositol 1,4,5-trisphosphate binding sites in the brain: regional distribution, characterization, and alterations in brains of patients with Parkinson's disease.
abstract: [3H]Inositol 1,4,5-trisphosphate [( 3H]Ins-(1,4,5)P3) binding studies were done on the human brain obtained at autopsy. The specific [3H]Ins(1,3,4,5)P3 binding sites in the cerebral and cerebellar cortices consisted of a single component with a high affinity (Kd = 11.3 and 16.5 nM, Bmax = 0.8 and 6.4 pmol/mg protein, respectively). The binding of [3H]Ins(1,4,5)P3 was potently inhibited by Ins(1,4,5)P3, in a nanomolar concentration, while other inositol phosphates and inositol were either much less potent or did not inhibit binding. The binding sites for [3H]Ins(1,4,5)P3 were discretely localized and were in the order: cerebellum much greater than basal ganglia, cerebral cortex greater than rhinencephalon greater than diencephalon, mesencephalon. There was an age-related loss of [3H]Ins(1,4,5)P3 binding in the frontal cortex. In the brains of patients with Parkinson's disease, [3H]Ins(1,4,5)P3 binding sites were reduced by about 50% in the caudate nucleus, putamen, and pallidum, while there were no differences in the frontal cortex, as compared to findings in the age-matched controls. Our findings suggest that [3H]Ins(1,4,5)P3 binding sites are closely linked to neural elements in the human brain.
authors.affiliation: Department of Pharmacology, Kobe University School of Medicine, Kobe, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kitamura
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: N
authors.initials: N
authors.lastname: Nishino
authors.forename: C
authors.initials: C
authors.lastname: Tanaka
mesh_terms: D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D015220:Calcium Channels; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D009928:Organ Specificity; D010300:Parkinson Disease / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D012016:Reference Values
chemical_list: D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate