Source:http://linkedlifedata.com/resource/pubmed/id/10581170
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| Predicate | Object |
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| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2000-1-6
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| pubmed:abstractText |
Neuropeptide Y (NPY) is known to induce robust feeding through the action of NPY receptors in the hypothalamus. Among the subtypes of NPY receptors, Y(1) receptors may play a key role in feeding regulation. In the present study, we demonstrated that a novel Y(1) antagonist, J-104870, shows high selectivity and potency for the Y(1) receptor with an anorexigenic effect on NPY-mediated feeding. J-104870 displaced [(125)I]peptide YY (PYY) binding to cloned human and rat Y(1) receptors with K(i) values of 0.29 and 0.54 nM, respectively, and inhibited the NPY (10 nM)-induced increase in intracellular calcium levels (IC(50) = 3.2 nM) in cells expressing human Y(1) receptors. In contrast, J-104870 showed low affinities for human Y(2) (K(i) > 10 microM), Y(4) (K(i) > 10 microM), and Y(5) receptors (K(i) = 6 microM). In rat hypothalamic membranes, J-104870 also completely displaced the binding of [(125)I]1229U91, which is known to bind to the typical Y(1) receptor, with a high affinity (K(i) = 2.0 nM). Intracerebroventricular (ICV) injection of J-104870 (200 microg) significantly suppressed NPY (5 microg)-induced feeding in satiated Sprague-Dawley rats by 74%. Furthermore, ICV and oral administration of J-104870 (200 microg and 100 mg/kg, respectively) significantly suppressed spontaneous food intake in Zucker fatty rats. These findings suggested that J-104870 is a selective and potent nonpeptide Y(1) antagonist with oral bioavailability and brain penetrability. In addition, the anorexigenic effect of J-104870 clearly revealed the participation of the Y(1) receptor in NPY-mediated feeding regulation. The potent and orally active Y(1) antagonist J-104970 is a useful tool for elucidating the physiological roles of NPY in obesity.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carbamates,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptide Y,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neuropeptide Y,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/neuropeptide Y-Y1 receptor
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0006-291X
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 1999 Academic Press.
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| pubmed:issnType |
Print
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| pubmed:day |
9
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| pubmed:volume |
266
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
88-91
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| pubmed:dateRevised |
2005-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10581170-Administration, Oral,
pubmed-meshheading:10581170-Animals,
pubmed-meshheading:10581170-Binding, Competitive,
pubmed-meshheading:10581170-Biological Availability,
pubmed-meshheading:10581170-Brain,
pubmed-meshheading:10581170-CHO Cells,
pubmed-meshheading:10581170-Carbamates,
pubmed-meshheading:10581170-Cell Membrane,
pubmed-meshheading:10581170-Cricetinae,
pubmed-meshheading:10581170-Feeding Behavior,
pubmed-meshheading:10581170-Hippocampus,
pubmed-meshheading:10581170-Humans,
pubmed-meshheading:10581170-Inhibitory Concentration 50,
pubmed-meshheading:10581170-Injections, Intraventricular,
pubmed-meshheading:10581170-Male,
pubmed-meshheading:10581170-Neuropeptide Y,
pubmed-meshheading:10581170-Rats,
pubmed-meshheading:10581170-Rats, Sprague-Dawley,
pubmed-meshheading:10581170-Rats, Zucker,
pubmed-meshheading:10581170-Receptors, Neuropeptide Y,
pubmed-meshheading:10581170-Thiazoles,
pubmed-meshheading:10581170-Time Factors
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| pubmed:year |
1999
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| pubmed:articleTitle |
The novel neuropeptide Y Y(1) receptor antagonist J-104870: a potent feeding suppressant with oral bioavailability.
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| pubmed:affiliation |
Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba, 300-2611, Japan. kantniak@banyu.co.jp
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| pubmed:publicationType |
Journal Article
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