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Receptor subtypes Y 1 and Y 5 mediate neuropeptide Y induced feeding in the guinea‐pig
Author(s) -
Lecklin Anne,
Lundell Ingrid,
Paananen Leena,
Wikberg Jarl E S,
Männistö Pekka T,
Larhammar Dan
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704667
Subject(s) - neuropeptide y receptor , receptor , medicine , endocrinology , peptide yy , guinea pig , antagonist , receptor antagonist , biology , chemistry , neuropeptide
Neuropeptide Y (NPY) is one of the most potent stimulants of food intake. It has been debated which receptor subtype mediates this response. Initially Y 1 was proposed, but later Y 5 was announced as a ‘feeding’ receptor in rats and mice. Very little is known regarding other mammals. The present study attempts to characterize the role of NPY in feeding behaviour in the distantly related guinea‐pig. When infused intracerebroventricularly, NPY dose‐dependently increased food intake. PYY, (Leu 31 ,Pro 34 )NPY and NPY(2 – 36) stimulated feeding, whereas NPY(13 – 36) had no effect. These data suggest that either Y 1 or Y 5 receptors or both may mediate NPY induced food intake in guinea‐pigs. The Y 1 receptor antagonists, BIBO 3304 and H 409/22 displayed nanomolar affinity for the Y 1 receptor ( K i values 1.1±0.2 n M and 5.6±0.9 n M , respectively), but low affinity for the Y 2 or Y 5 receptors. When guinea‐pigs were pretreated with BIBO 3304 and H 409/22, the response to NPY was inhibited. The Y 5 antagonist, CGP 71683A had high affinity for the Y 5 receptor ( K i 1.3±0.05 n M ) without having any significant activities at the Y 1 and Y 2 receptors. When CGP 71683A was infused into brain ventricles, the feeding response to NPY was attenuated. The present study shows that NPY stimulates feeding in guinea‐pigs through Y 1 and Y 5 receptors. As the guinea‐pig is very distantly related to the rat and mouse, this suggests that both Y 1 and Y 5 receptors may mediate NPY‐induced hyperphagia also in other orders of mammals.British Journal of Pharmacology (2002) 135 , 2029–2037; doi: 10.1038/sj.bjp.0704667