A novel subtype of the prostacyclin receptor expressed in the central nervous system

Hajime Takechi, Kiyoshi Matsumura, Yumiko Watanabe, Koichi Kato, Ryoji Noyori, Masaaki Suzuki, Yasuyoshi Watanabe

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

By use of several prostacyclin analogs and an in vitro autoradiographic technique, we have found a novel subtype of the prostacyclin receptor, one having different binding properties compared with those of the known prostacyclin receptor in the rat brain. Isocarbacyclin, which is a potent agonist for the known prostacyclin receptor, had high affinity for the novel subtype (dissociation constant (K(d)) of 7.8 nM). However, iloprost, which is usually used as a stable prostacyclin analog, showed low affinity binding (K(d) = 159 nM) for the subtype. Other prostaglandins showed no or little affinity for the subtype. [3H]Isocarbacyclin binding was high in the thalamus, lateral septal nucleus, hippocampus, cerebral cortex, striatum, and dorsal cochlear nucleus. Although the nucleus of the solitary tract and the spinal trigeminal nucleus showed a high density of [3H]isocarbacyclin binding, [3H]iloprost also had high affinity in these regions, and the binding specificity was similar to that for the known prostacyclin receptor. Hemilesion studies of striatal neurons lesioned by kainate or of dopaminergic afferents lesioned by 6-hydroxydopamine revealed that the binding sites of the novel subtype exist on neuronal cells in the striatum, but not on the presynaptic terminal of afferents or on glial cells. Electrophysiological studies carried out in the CA1 region of the hippocampus revealed that prostacyclin analogs have a facilitatory effect on the excitatory transmission through the novel prostacyclin receptor. The widespread expression of the prostacyclin receptor in the central nervous system suggests that prostacyclin has important roles in neuronal activity.

Original languageEnglish
Pages (from-to)5901-5906
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number10
DOIs
Publication statusPublished - 08-03-1996

Fingerprint

Epoprostenol Receptors
9-O-methanoprostaglandin I
Neurology
Central Nervous System
Epoprostenol
Iloprost
Hippocampus
Spinal Trigeminal Nucleus
Cochlear Nucleus
Corpus Striatum
Septal Nuclei
Solitary Nucleus
Kainic Acid
Oxidopamine
Presynaptic Terminals
Thalamus
Neuroglia
Cerebral Cortex
Neurons
Prostaglandins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Takechi, H., Matsumura, K., Watanabe, Y., Kato, K., Noyori, R., Suzuki, M., & Watanabe, Y. (1996). A novel subtype of the prostacyclin receptor expressed in the central nervous system. Journal of Biological Chemistry, 271(10), 5901-5906. https://doi.org/10.1074/jbc.271.10.5901
Takechi, Hajime ; Matsumura, Kiyoshi ; Watanabe, Yumiko ; Kato, Koichi ; Noyori, Ryoji ; Suzuki, Masaaki ; Watanabe, Yasuyoshi. / A novel subtype of the prostacyclin receptor expressed in the central nervous system. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 10. pp. 5901-5906.
@article{fe44c432ae914ceab9ee89fe8b4307b5,
title = "A novel subtype of the prostacyclin receptor expressed in the central nervous system",
abstract = "By use of several prostacyclin analogs and an in vitro autoradiographic technique, we have found a novel subtype of the prostacyclin receptor, one having different binding properties compared with those of the known prostacyclin receptor in the rat brain. Isocarbacyclin, which is a potent agonist for the known prostacyclin receptor, had high affinity for the novel subtype (dissociation constant (K(d)) of 7.8 nM). However, iloprost, which is usually used as a stable prostacyclin analog, showed low affinity binding (K(d) = 159 nM) for the subtype. Other prostaglandins showed no or little affinity for the subtype. [3H]Isocarbacyclin binding was high in the thalamus, lateral septal nucleus, hippocampus, cerebral cortex, striatum, and dorsal cochlear nucleus. Although the nucleus of the solitary tract and the spinal trigeminal nucleus showed a high density of [3H]isocarbacyclin binding, [3H]iloprost also had high affinity in these regions, and the binding specificity was similar to that for the known prostacyclin receptor. Hemilesion studies of striatal neurons lesioned by kainate or of dopaminergic afferents lesioned by 6-hydroxydopamine revealed that the binding sites of the novel subtype exist on neuronal cells in the striatum, but not on the presynaptic terminal of afferents or on glial cells. Electrophysiological studies carried out in the CA1 region of the hippocampus revealed that prostacyclin analogs have a facilitatory effect on the excitatory transmission through the novel prostacyclin receptor. The widespread expression of the prostacyclin receptor in the central nervous system suggests that prostacyclin has important roles in neuronal activity.",
author = "Hajime Takechi and Kiyoshi Matsumura and Yumiko Watanabe and Koichi Kato and Ryoji Noyori and Masaaki Suzuki and Yasuyoshi Watanabe",
year = "1996",
month = "3",
day = "8",
doi = "10.1074/jbc.271.10.5901",
language = "English",
volume = "271",
pages = "5901--5906",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "10",

}

Takechi, H, Matsumura, K, Watanabe, Y, Kato, K, Noyori, R, Suzuki, M & Watanabe, Y 1996, 'A novel subtype of the prostacyclin receptor expressed in the central nervous system', Journal of Biological Chemistry, vol. 271, no. 10, pp. 5901-5906. https://doi.org/10.1074/jbc.271.10.5901

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

In: Journal of Biological Chemistry, Vol. 271, No. 10, 08.03.1996, p. 5901-5906.

Research output: Contribution to journalArticle

TY - JOUR

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

AU - Takechi, Hajime

AU - Matsumura, Kiyoshi

AU - Watanabe, Yumiko

AU - Kato, Koichi

AU - Noyori, Ryoji

AU - Suzuki, Masaaki

AU - Watanabe, Yasuyoshi

PY - 1996/3/8

Y1 - 1996/3/8

N2 - By use of several prostacyclin analogs and an in vitro autoradiographic technique, we have found a novel subtype of the prostacyclin receptor, one having different binding properties compared with those of the known prostacyclin receptor in the rat brain. Isocarbacyclin, which is a potent agonist for the known prostacyclin receptor, had high affinity for the novel subtype (dissociation constant (K(d)) of 7.8 nM). However, iloprost, which is usually used as a stable prostacyclin analog, showed low affinity binding (K(d) = 159 nM) for the subtype. Other prostaglandins showed no or little affinity for the subtype. [3H]Isocarbacyclin binding was high in the thalamus, lateral septal nucleus, hippocampus, cerebral cortex, striatum, and dorsal cochlear nucleus. Although the nucleus of the solitary tract and the spinal trigeminal nucleus showed a high density of [3H]isocarbacyclin binding, [3H]iloprost also had high affinity in these regions, and the binding specificity was similar to that for the known prostacyclin receptor. Hemilesion studies of striatal neurons lesioned by kainate or of dopaminergic afferents lesioned by 6-hydroxydopamine revealed that the binding sites of the novel subtype exist on neuronal cells in the striatum, but not on the presynaptic terminal of afferents or on glial cells. Electrophysiological studies carried out in the CA1 region of the hippocampus revealed that prostacyclin analogs have a facilitatory effect on the excitatory transmission through the novel prostacyclin receptor. The widespread expression of the prostacyclin receptor in the central nervous system suggests that prostacyclin has important roles in neuronal activity.

AB - By use of several prostacyclin analogs and an in vitro autoradiographic technique, we have found a novel subtype of the prostacyclin receptor, one having different binding properties compared with those of the known prostacyclin receptor in the rat brain. Isocarbacyclin, which is a potent agonist for the known prostacyclin receptor, had high affinity for the novel subtype (dissociation constant (K(d)) of 7.8 nM). However, iloprost, which is usually used as a stable prostacyclin analog, showed low affinity binding (K(d) = 159 nM) for the subtype. Other prostaglandins showed no or little affinity for the subtype. [3H]Isocarbacyclin binding was high in the thalamus, lateral septal nucleus, hippocampus, cerebral cortex, striatum, and dorsal cochlear nucleus. Although the nucleus of the solitary tract and the spinal trigeminal nucleus showed a high density of [3H]isocarbacyclin binding, [3H]iloprost also had high affinity in these regions, and the binding specificity was similar to that for the known prostacyclin receptor. Hemilesion studies of striatal neurons lesioned by kainate or of dopaminergic afferents lesioned by 6-hydroxydopamine revealed that the binding sites of the novel subtype exist on neuronal cells in the striatum, but not on the presynaptic terminal of afferents or on glial cells. Electrophysiological studies carried out in the CA1 region of the hippocampus revealed that prostacyclin analogs have a facilitatory effect on the excitatory transmission through the novel prostacyclin receptor. The widespread expression of the prostacyclin receptor in the central nervous system suggests that prostacyclin has important roles in neuronal activity.

UR - http://www.scopus.com/inward/record.url?scp=0029916559&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029916559&partnerID=8YFLogxK

U2 - 10.1074/jbc.271.10.5901

DO - 10.1074/jbc.271.10.5901

M3 - Article

C2 - 8621463

AN - SCOPUS:0029916559

VL - 271

SP - 5901

EP - 5906

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 10

ER -