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Inositol 1,4,5-trisphosphate binding sites in the brain: Regional distribution, characterization, and alterations in brains of patients with Parkinson's disease

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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 (K d =11.3 and 16.5 nM,B max=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 nuch 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 ≫basal ganglia, cerebral cortex>rhinencephalon>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 agematched controls. Our findings suggest that [3H]Ins-(1,4,5)P3 binding sites are closely linked to neural elements in the human brain.

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Authors and Affiliations

  1. Department of Pharmacology, Kobe University School of Medicine, 7-5-4 Kusunoki-cho, Chuo-ku, 650, Kobe, Japan

    Noboru Kitamura, Takeshi Hashimoto, Naoki Nishino & Chikako Tanaka

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  1. Noboru Kitamura
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  2. Takeshi Hashimoto
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  3. Naoki Nishino
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  4. Chikako Tanaka
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Kitamura, N., Hashimoto, T., Nishino, N. et al. Inositol 1,4,5-trisphosphate binding sites in the brain: Regional distribution, characterization, and alterations in brains of patients with Parkinson's disease. J Mol Neurosci 1, 181–187 (1989). https://doi.org/10.1007/BF02918905

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