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Age-related changes of the binding of [3H]SA4503 to sigma1 receptors in the rat brain

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Abstract

We have recently developed 1-([3-O-methyl-11C]3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine ([11C]SA4503) as a selective radioligand for mapping sigma1 receptors in the brain by positron emission tomography (PET). In the present short communication we evaluated the agerelated changes of the binding of this ligand to sigma1 receptors in Fisher-344 rats (1.5-, 6-, 12-, and 24-month-old) by thein vitro binding assay. We also measured the binding of [3H](+)-pentazocine to sigma1 receptors and the binding of [3H]1,3-di-O-tolylguanidine to sigma2 receptors, which are current standard methods. The specific binding of the three radioligands increased age-dependently. Both Kd and Bmax values of the 24-month-old rats for each radioligand were significantly higher than those of the young rats (1.5- and 6-month-old). The increased numbers of both sigma1 and sigma2 receptor subtypes in the aged rats compensate for the lowered affinity, and rather enhanced the radioligand-receptor binding. The results contrast strikingly with the age-dependent decrease in the dopaminergic, cholinergic and glutamatergic receptors that are reported to be correlated with the sigma receptors, and indicate that a PET study with [11C]SA4503 to evaluate the aging process in humans would be of great interest.

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Authors and Affiliations

  1. Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Nakacho, Itabashi-ku, 173-0022, Tokyo, Japan

    Kiichi Ishiwata, Tadayuki Kobayashi & Kazunori Kawamura

  2. M’s Sciences Co., Japan

    Tadayuki Kobayashi

  3. SHI Accelerator Service Co. Ltd., Tokyo, Japan

    Kazunori Kawamura & Kiyoshi Matsuno

Authors
  1. Kiichi Ishiwata
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  2. Tadayuki Kobayashi
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  3. Kazunori Kawamura
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  4. Kiyoshi Matsuno
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Correspondence to Kiichi Ishiwata.

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M's Science Co.

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Ishiwata, K., Kobayashi, T., Kawamura, K. et al. Age-related changes of the binding of [3H]SA4503 to sigma1 receptors in the rat brain. Ann Nucl Med 17, 73–77 (2003). https://doi.org/10.1007/BF02988264

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  • DOI: https://doi.org/10.1007/BF02988264

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