Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1).
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.
Bächner
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D
Institut für Zellbiochemie und klinische Neurobiologie, Universität Hamburg, Martinistrasse 52, 20246, Hamburg, Germany.
Kreienkamp
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H
Weise
C
C
Buck
F
F
Richter
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007028:Hypothalamic Hormones / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D008024:Ligands; D013058:Mass Spectrometry; D008543:Melanins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D010907:Pituitary Hormones / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014020:Tissue Extracts / Q000378:metabolism; D014981:Xenopus
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D007028:Hypothalamic Hormones; D008024:Ligands; C491208:MCHR1 protein, rat; D008543:Melanins; D010907:Pituitary Hormones; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; D014020:Tissue Extracts; C019463:melanin-concentrating hormone; D019204:GTP-Binding Proteins