共 23 条
L-152,804: Orally active and selective neuropeptide YY5 receptor antagonist
被引:117
作者:

Kanatani, A
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Ishihara, A
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Iwaasa, H
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Nakamura, K
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Okamoto, O
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Hidaka, M
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Ito, J
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Fukuroda, T
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

MacNeil, DJ
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Van der Ploeg, LHT
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Ishii, Y
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Okabe, T
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Fukami, T
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Ihara, M
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h-index: 0
机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan
机构:
[1] Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan
[2] Merck & Co Inc, Merck Res Labs, Rahway, NJ 07065 USA
关键词:
D O I:
10.1006/bbrc.2000.2696
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:
Neuropeptide Y (NPY) elicits food intake through the action of hypothalamic G-protein-coupled receptors. Previous publications indicate that the Y5 receptor may represent one of these postulated hypothalamic "feeding" receptors. Using a potent and orally available Y5 antagonist L-152,804, we evaluated the involvement of the Y5 receptor in feeding regulation. L-152,804 displaced [I-125]peptide YY (PYY) binding to human and rat Y5 receptors with K-i values of 26 and 31 nM, respectively, and inhibited NPY (100 nM)-induced increase in intracellular calcium levels via human Y5 receptors (IC50 = 210 nM). L-152,804 did not show significant affinity for human Y1, Y2, and Y4 receptors at a dose of 10 mu M. Intracerebroventricular (ICV) (30 mu g) or oral (10 mg/kg) administration of L-152,804 significantly inhibited food intake evoked by ICV-injected bovine pancreatic peptide (bPP, 5 mu g; a moderately selective Y4, Y5 agonist) in satiated SD rats. However L-152,804 did not significantly inhibit ICV NPY (5 mu g; a Y1, Y2, Y5 agonist)-induced food intake. These findings suggest that L-152,804 is a selective and potent nonpeptide Y5 antagonist with oral bioavailability and brain penetrability. In addition, the anorexigenic effects of L-152,804 on bPP-induced feeding revealed participation of the Y5 receptor in feeding regulation, while ICV administration of NPY does not appear to significantly contribute to Y5 stimulated food intake. We conclude that the potent and orally active Y5 antagonist, L-152,804, represents a useful tool to address the physiological role of the Y5 receptor. (C) 2000 Academic Press.
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页码:169 / 173
页数:5
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MacNeil, DJ
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Merck Res Labs, Tsukuba, Ibaraki 3002611, Japan

Van der Ploeg, LHT
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Merck Res Labs, Tsukuba, Ibaraki 3002611, Japan

Saga, Y
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Merck Res Labs, Tsukuba, Ibaraki 3002611, Japan

Nishimura, S
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Merck Res Labs, Tsukuba, Ibaraki 3002611, Japan

Ihara, M
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机构: Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Merck Res Labs, Tsukuba, Ibaraki 3002611, Japan
[9]
Potent neuropeptide YY1 receptor antagonist, 1229U91: Blockade of neuropeptide Y-induced and physiological food intake
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1996, 137 (08)
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Kanatani, A
论文数: 0 引用数: 0
h-index: 0

Ishihara, A
论文数: 0 引用数: 0
h-index: 0

Asahi, S
论文数: 0 引用数: 0
h-index: 0

Tanaka, T
论文数: 0 引用数: 0
h-index: 0

Ozaki, S
论文数: 0 引用数: 0
h-index: 0

Ihara, M
论文数: 0 引用数: 0
h-index: 0
[10]
The novel neuropeptide YY1 receptor antagonist J-104870:: A potent feeding suppressant with oral bioavailability
[J].
Kanatani, A
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Kanno, T
;
Ishihara, A
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Hata, M
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Sakuraba, A
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Tanaka, T
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;
Mase, T
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Fukami, T
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Ihara, M
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,
1999, 266 (01)
:88-91

Kanatani, A
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机构:
Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Kanno, T
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Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Ishihara, A
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Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Hata, M
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Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Sakuraba, A
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Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Tanaka, T
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Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Tsuchiya, Y
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Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Mase, T
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Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Fukuroda, T
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机构:
Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Fukami, T
论文数: 0 引用数: 0
h-index: 0
机构:
Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

Ihara, M
论文数: 0 引用数: 0
h-index: 0
机构:
Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan