A novel subtype of prostacyclin receptor in the central nervous system

Yumiko Watanabe, Kiyoshi Matsumura, Hajime Takechi, Koichi Kato, Hiroshi Morii, Margareta Björkman, Bengt Långström, Ryoji Noyori, Masaaki Suzuki, Yasuyoshi Watanabe

Research output: Contribution to journalArticle

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Abstract

Recently, in the course of our search for the prostacyclin receptor in the brain, we found a novel subtype, designated as IP2, which was finely discriminated by use of the specific ligand (15R)-16-m-tolyl-17,18,19,20- tetranorisocarbacyclin (15R-TIC) and specifically localized in the rostral part of the brain. In the present study, the tritiated compound 15R-[15- 3H]TIC was synthesized and utilized for more specific research on IP2. The specificity of binding to rat brain regions was confirmed by use of several prostacyclin derivatives including 15S-TIC. Mapping of 15R- and 15S[3H]TIC binding in adjacent pairs of frozen sections of rat brain demonstrated a quite similar pattern of distribution in almost all rostral brain regions, indicating that the regions may contain only the IP2 subtype. On the other hand, 15R-[3H]TIC binding was very faint as compared with 15S-[3H]TIC binding in the caudal medullary region. High densities of 15R-[3H]TIC binding sites were shown in the dorsal part of the lateral septal nucleus, thalamic nuclei, limbic structures, and some of the cortical regions. Scatchard plot analysis showed two components of high-affinity 15R-[3H]TIC binding in the rostral regions, one with a K(D) value at ~1 nM and the other with ~30 nM. These results strengthen our previous finding that a different subtype of prostacyclin receptor is expressed in the CNS, and the map with 15R-[3H]TIC obtained here could guide further studies on the molecular and functional properties of the IP2.

Original languageEnglish
Pages (from-to)2583-2592
Number of pages10
JournalJournal of Neurochemistry
Volume72
Issue number6
DOIs
Publication statusPublished - 03-06-1999

Fingerprint

Epoprostenol Receptors
Neurology
Brain
Central Nervous System
Rats
Thalamic Nuclei
Septal Nuclei
Frozen Sections
Epoprostenol
Binding Sites
Ligands
Derivatives
Research

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Watanabe, Y., Matsumura, K., Takechi, H., Kato, K., Morii, H., Björkman, M., ... Watanabe, Y. (1999). A novel subtype of prostacyclin receptor in the central nervous system. Journal of Neurochemistry, 72(6), 2583-2592. https://doi.org/10.1046/j.1471-4159.1999.0722583.x
Watanabe, Yumiko ; Matsumura, Kiyoshi ; Takechi, Hajime ; Kato, Koichi ; Morii, Hiroshi ; Björkman, Margareta ; Långström, Bengt ; Noyori, Ryoji ; Suzuki, Masaaki ; Watanabe, Yasuyoshi. / A novel subtype of prostacyclin receptor in the central nervous system. In: Journal of Neurochemistry. 1999 ; Vol. 72, No. 6. pp. 2583-2592.
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Watanabe, Y, Matsumura, K, Takechi, H, Kato, K, Morii, H, Björkman, M, Långström, B, Noyori, R, Suzuki, M & Watanabe, Y 1999, 'A novel subtype of prostacyclin receptor in the central nervous system', Journal of Neurochemistry, vol. 72, no. 6, pp. 2583-2592. https://doi.org/10.1046/j.1471-4159.1999.0722583.x

A novel subtype of prostacyclin receptor in the central nervous system. / Watanabe, Yumiko; Matsumura, Kiyoshi; Takechi, Hajime; Kato, Koichi; Morii, Hiroshi; Björkman, Margareta; Långström, Bengt; Noyori, Ryoji; Suzuki, Masaaki; Watanabe, Yasuyoshi.

In: Journal of Neurochemistry, Vol. 72, No. 6, 03.06.1999, p. 2583-2592.

Research output: Contribution to journalArticle

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T1 - A novel subtype of prostacyclin receptor in the central nervous system

AU - Watanabe, Yumiko

AU - Matsumura, Kiyoshi

AU - Takechi, Hajime

AU - Kato, Koichi

AU - Morii, Hiroshi

AU - Björkman, Margareta

AU - Långström, Bengt

AU - Noyori, Ryoji

AU - Suzuki, Masaaki

AU - Watanabe, Yasuyoshi

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Y1 - 1999/6/3

N2 - Recently, in the course of our search for the prostacyclin receptor in the brain, we found a novel subtype, designated as IP2, which was finely discriminated by use of the specific ligand (15R)-16-m-tolyl-17,18,19,20- tetranorisocarbacyclin (15R-TIC) and specifically localized in the rostral part of the brain. In the present study, the tritiated compound 15R-[15- 3H]TIC was synthesized and utilized for more specific research on IP2. The specificity of binding to rat brain regions was confirmed by use of several prostacyclin derivatives including 15S-TIC. Mapping of 15R- and 15S[3H]TIC binding in adjacent pairs of frozen sections of rat brain demonstrated a quite similar pattern of distribution in almost all rostral brain regions, indicating that the regions may contain only the IP2 subtype. On the other hand, 15R-[3H]TIC binding was very faint as compared with 15S-[3H]TIC binding in the caudal medullary region. High densities of 15R-[3H]TIC binding sites were shown in the dorsal part of the lateral septal nucleus, thalamic nuclei, limbic structures, and some of the cortical regions. Scatchard plot analysis showed two components of high-affinity 15R-[3H]TIC binding in the rostral regions, one with a K(D) value at ~1 nM and the other with ~30 nM. These results strengthen our previous finding that a different subtype of prostacyclin receptor is expressed in the CNS, and the map with 15R-[3H]TIC obtained here could guide further studies on the molecular and functional properties of the IP2.

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