NPY-induced feeding involves the action of a Y1-like receptor in rodents.
We have reported that the potent peptidic Y1 antagonist, 1229U91, significantly suppressed NPY-induced and spontaneous feeding [32,33]. However, information on the precise selectivity of 1229U91 for NPY receptors is lacking. The Y5 receptor has been considered a key receptor for feeding regulation. In the present study we showed that 1229U91 has high affinities for the human and rat Y1 receptors (Ki = 0.041 nM and 0.16 nM, respectively) and also a high affinity for the human Y4 receptor (Ki = 0.33 nM), whereas it shows moderate affinities for the human Y2, Y5 and rat Y5 receptors (K values of 20-170 nM). Moreover, 1229U91 potently inhibits NPY-induced [Ca2+]i increases in cells expressing human Y1 receptors. In contrast, 1229U91 is an agonist at other NPY receptors like the Y2, Y4 and Y5 receptors. Intracerebroventricular (i.c.v.)-injected 1229U91 (30 microg/head) significantly suppressed human NPY-induced feeding in SD rats, while 1229U91 only moderately inhibited bovine pancreatic polypeptide (bPP; an in vivo Y5 agonist)-induced feeding. These results indicate that the food intake evoked by NPY might be mediated by the Y1 receptor, rather than the Y5 receptor. Thus, the Y1 receptor or possibly a novel Y1-like receptor sensitive to 1229U91 may play a key role in the regulation of NPY-induced feeding.
Kanatani
A
A
Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo, Japan. kantniak@banyu.co.jp
Ito
J
J
Ishihara
A
A
Iwaasa
H
H
Fukuroda
T
T
Fukami
T
T
MacNeil
D J
DJ
Van der Ploeg
L H
LH
Ihara
M
M
D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002417:Cattle; D002460:Cell Line; D006224:Cricetinae; D004435:Eating / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology* / Q000502:physiology; D010191:Pancreatic Polypeptide / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology*
C097287:1229U91; D009478:Neuropeptide Y; D010456:Peptides, Cyclic; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C100568:neuropeptide Y5 receptor; D010191:Pancreatic Polypeptide