Add time:08/27/2019         Source:sciencedirect.com

Neuropeptide Y has potent appetite stimulating effects which are mediated by hypothalamic receptors believed to be of the neuropeptide Y Y1 and/or neuropeptide Y Y5 subtype. In mice, the neuropeptide Y y6 receptor is also expressed in the hypothalamus, suggesting that it too may function as a feeding receptor in this species. Several laboratories have studied the pharmacology of the neuropeptide Y y6 receptor, but their results are not in agreement. Using neuropeptide Y and a variety of peptide analogs and small molecule antagonists, we have determined that the pharmacology of the cloned mouse neuropeptide Y y6 receptor is distinct from that of the other known neuropeptide Y receptors. The rank order of binding affinity for the mouse neuropeptide Y y6 receptor is [(Ile,Glu,Pro,Dpr,Tyr,Arg,Leu,Arg,Tyr–NH2)2 cyclic (2,4′),(2′,4)-diamide] (1229U91)>human peptide YY=human, rat neuropeptide Y=human, rat neuropeptide Y-(2–36)=human, rat [Leu31, Pro34]neuropeptide Y>human, rat neuropeptide Y-(3–36)>human, rat neuropeptide Y-(13–36)>porcine (Cys2)-neuropeptide Y-(1–4)-8-aminooctanoyl-(d-Cys27)-neuropeptide Y-(25–32) (C2–neuropeptide Y)>porcine [d-Trp32]neuropeptide Y>rat pancreatic polypeptide=human pancreatic polypeptide. A similar rank order of potency is seen for inhibition of forskolin-stimulated cyclic AMP. The neuropeptide Y Y5 receptor antagonist trans-naphthalene-1-sulfonic acid {4-[4-amino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl}-amide hydrochloride (CGP 71683A) and the neuropeptide Y Y1 receptor antagonist ((R)-N2-diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-argininamide) (BIBP3226) bind weakly to the neuropeptide Y y6 receptor (Ki 2255±197 nM and >10,000 nM, respectively). Although the function of the neuropeptide Y y6 receptor remains to be elucidated, its pharmacology is not consistent with a role in appetite regulation.

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