Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin‐like receptor 1 (SLC‐1)

FEBS Letters

Bächner, Dietmar²  Weise, Christoph¹  Kreienkamp, Hans-Jürgen²  Buck, Friedrich²  Richter, Dietmar² 

[1] Institut für Chemie-Biochemie, Freie Universität Berlin, Thielallee 63, 14195 Berlin, Germany;Institut für Zellbiochemie und klinische Neurobiologie, Universität Hamburg, Martinistrasse 52, 20246 Hamburg, Germany

关键词: Somatostatin;    Melanin concentrating hormone receptor;    Reverse physiology;    Neuropeptide;    Food intake behavior;    MCH;    melanin concentrating hormone;    SLC-1;    somatostatin-like receptor 1;    GPCR;    G protein-coupled receptor;    GIRK;    G protein-gated inwardly rectifying potassium channel;    HPLC;    high performance liquid chromatography;    hK;    high K+ medium;    SST14;    somatostatin-14;    SST28;    somatostatin-28;   

DOI  :  10.1016/S0014-5793(99)01092-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

To identify possible ligands of the orphan somatostatin-like receptor 1 (SLC-1), rat brain extracts were analyzed by using the functional expression system of Xenopus oocytes injected with cRNAs encoding SLC-1 and G protein-gated inwardly rectifying potassium channels (GIRK). A strong inward current was observed with crude rat brain extracts which upon further purification by cation exchange chromatography and high performance liquid chromatography (HPLC) yielded two peptides with a high agonist activity. Mass spectrometry and partial peptide sequencing revealed that one peptide is identical with the neuropeptide melanin concentrating hormone (MCH), the other represents a truncated version of MCH lacking the three N-terminal amino acid residues. Xenopus oocytes expressing the MCH receptor responded to nM concentrations of synthetic MCH not only by the activation of GIRK-mediated currents but also by the induction of Ca²⁺ dependent chloride currents mediated by phospholipase C. This indicates that the MCH receptor can couple either to the G_i- or G_q-mediated signal transduction pathway, suggesting that MCH may serve for a number of distinct brain functions including food uptake behavior.

【 授权许可】

Unknown