Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Brain Chemistry*
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Chromatography, High Pressure Liquid
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Electrophysiology
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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Hypothalamic Hormones / isolation & purification
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Hypothalamic Hormones / metabolism*
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Hypothalamic Hormones / pharmacology
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Ligands
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Mass Spectrometry
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Melanins / isolation & purification
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Melanins / metabolism*
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Melanins / pharmacology
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Molecular Sequence Data
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Oocytes / physiology
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Pituitary Hormones / isolation & purification
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Pituitary Hormones / metabolism*
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Pituitary Hormones / pharmacology
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Potassium Channels / genetics
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Potassium Channels / metabolism
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Potassium Channels, Inwardly Rectifying*
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Rats
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Receptors, Somatostatin / genetics
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Receptors, Somatostatin / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Signal Transduction
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Tissue Extracts / metabolism
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Xenopus
Substances
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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Hypothalamic Hormones
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Ligands
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MCHR1 protein, rat
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Melanins
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Pituitary Hormones
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Receptors, Somatostatin
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Recombinant Proteins
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Tissue Extracts
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melanin-concentrating hormone
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GTP-Binding Proteins