Characterization of NPY receptors controlling lipolysis and leptin secretion in human adipocytes

FEBS Letters

Le Fur, Gérard¹  Lafontan, Max³  Serradeil-Le Gal, Claudine¹  Casellas, Pierre²  Marchand, Jean²  Pouzet, Brigitte¹  Pascal, Marc¹  Maffrand, Jean-Pierre¹  Raufaste, Danielle¹ 

[1] Sanofi-Synthelabo, 195 Route d'Espagne, 31036 Toulouse Cedex 05, France;Sanofi-Synthelabo, rue du Professeur J. Blayac, 34184 Montpellier Cedex 04, France;INSERM U317, Institut L. Bugnard, CHU Rangueil, 31054 Toulouse Cedex, France

关键词: Neuropeptide Y;    Peptide YY;    Human adipocyte;    Lipolysis;    Neuropeptide Y Y1 receptor;    Leptin;    NPY;    neuropeptide Y;    PYY;    peptide YY;    ADA;    adenosine deaminase;   

DOI  :  10.1016/S0014-5793(00)01649-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In order to characterize neuropeptide Y (NPY) receptors present in human adipocytes, we used selective ligands together with specific molecular probes able to recognize the different NPY receptor subtypes. RT-PCR experiments revealed the presence of Y₁ receptor transcripts with Y₄ and Y₅ and absence of Y₂ signals. Binding studies, using selective radioiodinated ligands, detected a high number (B _max=497±124 fmol/mg protein) of a high affinity binding site only with [¹²⁵I]peptide YY (PYY) and [¹²⁵I](Leu³¹,Pro³⁴)PYY. These sites exhibited a typical Y₁ profile as indicated by the rank order of affinity of NPY analogs and the high affinity of two selective NPY receptor antagonists, SR120819A and BIBP3226. In [³⁵S]GTPγS binding experiments, PYY activation was totally inhibited by SR120819A and BIBP3226. Both compounds antagonized, with similar efficiency, the antilipolytic effect exerted by NPY in isolated adipocytes. Finally, PYY and Y₁ ligands enhanced adipocyte leptin secretion, an effect totally prevented by SR120819A. Thus, highly expressed in human adipocytes, the Y₁ receptor sustains the strong antilipolytic effect of NPY and exerts a positive action on leptin secretion.

【 授权许可】

Unknown