Molecular identification of nicotinic acid receptor

被引：288

作者：

Soga, T ^{[1
]}

Kamohara, M ^{[1
]}

Takasaki, J ^{[1
]}

Matsumoto, S ^{[1
]}

Saito, T ^{[1
]}

Ohishi, T ^{[1
]}

Hiyama, H ^{[1
]}

Matsuo, A ^{[1
]}

Matsushime, H ^{[1
]}

Furuichi, K ^{[1
]}

机构：

[1] Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, Mol Med Labs, Tsukuba, Ibaraki 3058585, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 303卷 / 01期

关键词：

G-protein-coupled receptor; nicotinic acid; Acipimox; adipose;

D O I：

10.1016/S0006-291X(03)00342-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 GTPgammaS binding in a dose-dependent manner. [H-3]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. (C) 2003 Elsevier Science (USA). All rights reserved.

引用

页码：364 / 369

页数：6

共 20 条

[1] NICOTINIC-ACID INHIBITS ADIPOCYTE ADENYLATE-CYCLASE IN A HORMONE-LIKE MANNER [J].