title: Molecular identification of nicotinic acid receptor.
abstract: Nicotinic acid and its derivative, Acipimox, have been widely used in the treatment of hyperlipidemia. Pharmacological studies have demonstrated that they exert the beneficial effect through the activation of a Gi-protein-coupled receptor on adipocyte, which has remained elusive to date. Here we show that a novel GPCR, designated HM74b because of its high similarity to HM74, is a receptor for nicotinic acid. HM74b mRNA is found in human, murine, and rat adipose tissues. Nicotinic acid and Acipimox inhibit forskolin-stimulated intracellular cAMP accumulation in human HM74b-expressing cells and activate GTP gamma S binding in a dose-dependent manner. [3H]Nicotinic acid specifically binds to HM74b-expressing membrane and its binding is replaced by Acipimox. This finding will open a new phase of research on the physiological role of nicotinic acid and will be a clue to develop novel antihyperlipidemic drugs.
authors.affiliation: Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Soga
authors.forename: Masazumi
authors.initials: M
authors.lastname: Kamohara
authors.forename: Jun
authors.initials: J
authors.lastname: Takasaki
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Tetsu
authors.initials: T
authors.lastname: Saito
authors.forename: Takahide
authors.initials: T
authors.lastname: Ohishi
authors.forename: Hideki
authors.initials: H
authors.lastname: Hiyama
authors.forename: Ayako
authors.initials: A
authors.lastname: Matsuo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Matsushime
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Furuichi
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009525:Niacin / Q000494:pharmacology; D016366:Open Reading Frames; D011061:Poly A; D011719:Pyrazines / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D011719:Pyrazines; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D005576:Colforsin; D011061:Poly A; D009525:Niacin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000242:Cyclic AMP; C027696:acipimox