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Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin‐like receptor 1 (SLC‐1)
Author(s) -
Bächner Dietmar,
Kreienkamp Hans-Jürgen,
Weise Christoph,
Buck Friedrich,
Richter Dietmar
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01092-3
Subject(s) - melanin concentrating hormone , xenopus , g protein coupled inwardly rectifying potassium channel , chemistry , receptor , orphan receptor , somatostatin , somatostatin receptor , peptide , agonist , neuropeptide , biochemistry , medicine , g protein , endocrinology , biology , transcription factor , gene
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 Ca 2+ 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.