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A Novel Subtype of Prostacyclin Receptor in the Central Nervous System
Author(s) -
Watanabe Yumiko,
Matsumura Kiyoshi,
Takechi Hajime,
Kato Koichi,
Morii Hiroshi,
Björkman Margareta,
Langstrom Bengt,
Noyori Ryoji,
Suzuki Masaaki,
Watanabe Yasuyoshi
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722583.x
Subject(s) - prostacyclin , central nervous system , binding site , receptor , ligand (biochemistry) , neuroscience , nucleus , biology , chemistry , dorsum , medicine , microbiology and biotechnology , endocrinology , anatomy , biochemistry
Recently, in the course of our search for the prostacyclinreceptor in the brain, we found a novel subtype, designated as IP 2 ,which was finely discriminated by use of the specific ligand(15 R )‐16‐ m ‐tolyl‐17,18,19,20‐tetranorisocarbacyclin(15 R ‐TIC) and specifically localized in the rostral part of thebrain. In the present study, the tritiated compound15 R ‐[15‐ 3 H]TIC was synthesized and utilized for morespecific research on IP 2 . The specificity of binding to rat brainregions was confirmed by use of several prostacyclin derivatives including15 S ‐TIC. Mapping of 15 R ‐ and 15 S ‐[ 3 H]TICbinding in adjacent pairs of frozen sections of rat brain demonstrated a quitesimilar pattern of distribution in almost all rostral brain regions,indicating that the regions may contain only the IP 2 subtype. Onthe other hand, 15 R ‐[ 3 H]TIC binding was very faint ascompared with 15 S ‐[ 3 H]TIC binding in the caudal medullaryregion. High densities of 15 R ‐[ 3 H]TIC binding sites wereshown in the dorsal part of the lateral septal nucleus, thalamic nuclei,limbic structures, and some of the cortical regions. Scatchard plot analysisshowed two components of high‐affinity 15 R ‐[ 3 H]TIC bindingin the rostral regions, one with a K D value at ∼1n M and the other with ∼30 n M . These results strengthenour previous finding that a different subtype of prostacyclin receptor isexpressed in the CNS, and the map with 15 R ‐[ 3 H]TICobtained here could guide further studies on the molecular and functionalproperties of the IP 2 .