Effect of a selective neuropeptide Y Y(2) receptor antagonist, BIIE0246 on neuropeptide Y release.
We have examined the selective neuropeptide Y Y(2) receptor antagonist, (S)-N(2)-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b, e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl]cyclopentyl]acetyl ]-N-[2-[1 ,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3-H-1,2, 4-triazol-4-yl]ethyl]-argininamid (BIIE0246) on neuropeptide release from rat hypothalamic slices in vitro. BIIE0246 prevented neuropeptide Y-(13-36)-induced reduction in basal and K(+)-stimulated neuropeptide Y release. Addition of BIIE0246 alone enhanced K(+)-stimulated neuropeptide release, without affecting basal release. These data are consistent with anatomical and functional studies suggesting a pre-synaptic role for neuropeptide Y Y(2) receptors in regulating rat hypothalamic neuropeptide Y release in the rat.
King
P J
PJ
Diabetes and Endocrinology Research Group, Department of Medicine, University of Liverpool, Duncan Building, Daulby Street, L69 3GA, Liverpool, UK. p.j.king@liverpool.ac.uk
Williams
G
G
Doods
H
H
Widdowson
P S
PS
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*
D001552:Benzazepines; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D001120:Arginine; C403256:BIIE 0246; D011188:Potassium