PMID- 10872822
OWN - NLM
STAT- MEDLINE
DCOM- 20000717
LR  - 20051117
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 272
IP  - 1
DP  - 2000 May 27
TI  - L-152,804: orally active and selective neuropeptide Y Y5 receptor antagonist.
PG  - 169-73
AB  - 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 [125I]peptide YY 
      (PYY) binding to human and rat Y5 receptors with Ki 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 microM. 
      Intracerebroventricular (i.c.v.) (30 microg) or oral (10 mg/kg) administration of 
      L-152,804 significantly inhibited food intake evoked by i.c.v.-injected bovine 
      pancreatic peptide (bPP, 5 microg; a moderately selective Y4, Y5 agonist) in 
      satiated SD rats. However L-152,804 did not significantly inhibit i.c.v. NPY (5 
      microg; a Y1, Y2, Y5 agonist)-induced food intake. These findings suggest that 
      L-152,804 is a selective and potent non-peptide 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 i.c.v. 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.
FAU - Kanatani, A
AU  - Kanatani A
AD  - Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan.
FAU - Ishihara, A
AU  - Ishihara A
FAU - Iwaasa, H
AU  - Iwaasa H
FAU - Nakamura, K
AU  - Nakamura K
FAU - Okamoto, O
AU  - Okamoto O
FAU - Hidaka, M
AU  - Hidaka M
FAU - Ito, J
AU  - Ito J
FAU - Fukuroda, T
AU  - Fukuroda T
FAU - MacNeil, D J
AU  - MacNeil DJ
FAU - Van der Ploeg, L H
AU  - Van der Ploeg LH
FAU - Ishii, Y
AU  - Ishii Y
FAU - Okabe, T
AU  - Okabe T
FAU - Fukami, T
AU  - Fukami T
FAU - Ihara, M
AU  - Ihara M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cyclohexanes)
RN  - 0 (L 152804)
RN  - 0 (Neuropeptide Y)
RN  - 0 (Receptors, Neuropeptide Y)
RN  - 0 (Xanthenes)
RN  - 0 (neuropeptide Y5 receptor)
RN  - 59763-91-6 (Pancreatic Polypeptide)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - CHO Cells
MH  - COS Cells
MH  - Cattle
MH  - Cricetinae
MH  - Cyclohexanes/administration & dosage/*pharmacology
MH  - Eating/drug effects/physiology
MH  - Humans
MH  - Injections, Intraventricular
MH  - Male
MH  - Neuropeptide Y/pharmacology
MH  - Pancreatic Polypeptide/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Neuropeptide Y/*antagonists & inhibitors/physiology
MH  - Xanthenes/administration & dosage/*pharmacology
EDAT- 2000/06/29 11:00
MHDA- 2000/07/25 11:00
CRDT- 2000/06/29 11:00
PHST- 2000/06/29 11:00 [pubmed]
PHST- 2000/07/25 11:00 [medline]
PHST- 2000/06/29 11:00 [entrez]
AID - S0006-291X(00)92696-2 [pii]
AID - 10.1006/bbrc.2000.2696 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2000 May 27;272(1):169-73. doi: 
      10.1006/bbrc.2000.2696.