Isolation and identification of melanin-concentrating hormone as the endogenous ligand of the SLC-1 receptor.
Melanin-concentrating hormone (MCH), which is an orexigenic peptide, was isolated and identified as the endogenous ligand of the SLC-1 receptor. We established a CHO cell line expressing the rat SLC-1 receptor to search for its endogenous ligand. The extract of rat whole brain showed inhibition of intracellular forskolin-induced cAMP accumulation in rat SLC-1-expressing CHO cells and was purified. Using HPLC purification, we isolated and identified MCH as the endogenous ligand of the SLC-1 receptor. The authentic MCH demonstrated a dose-dependent inhibitory effect on cAMP accumulation in forskolin-stimulated rat and human SLC-1-expressing CHO cells with an EC(50) value of 0.2 nM for both the rat and human SLC-1 receptors. This is the first description of the functional receptor for MCH.
Shimomura
Y
Y
Pharmaceutical Discovery Research Division, Takeda Chemical Industries, Ltd., Wadai 10, Tsukuba, Ibaraki, 300-4293, Japan.
Mori
M
M
Sugo
T
T
Ishibashi
Y
Y
Abe
M
M
Kurokawa
T
T
Onda
H
H
Nishimura
O
O
Sumino
Y
Y
Fujino
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D016466:CHO Cells; D002851:Chromatography, High Pressure Liquid; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007028:Hypothalamic Hormones / Q000302:isolation & purification* / Q000378:metabolism*; D008024:Ligands; D008297:Male; D008543:Melanins / Q000302:isolation & purification* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010907:Pituitary Hormones / Q000302:isolation & purification* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D007028:Hypothalamic Hormones; D008024:Ligands; C103263:MCHR1 protein, human; C491208:MCHR1 protein, rat; D008543:Melanins; D010907:Pituitary Hormones; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; D005576:Colforsin; C019463:melanin-concentrating hormone; D000242:Cyclic AMP; D019204:GTP-Binding Proteins