Family

Melanin-concentrating hormone 1 receptor (IPR004047)

Short name: MCH1_rcpt

Family relationships

Description

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups [PMID: 12679517]. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [PMID: 8170923]. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [PMID: 8170923, PMID: 8081729, PMID: 15914470, PMID: 18948278, PMID: 16753280]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice [PMID: 12679517]. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [PMID: 23020293].

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [PMID: 2111655, PMID: 2830256, PMID: 8386361].

Melanin-concentrating hormone (MCH) is a cyclic peptide originally identified in teleost fish [PMID: 8170923]. In fish, MCH is released from the pituitary and causes lightening of skin pigment cells through pigment aggregation [PMID: 8170923, PMID: 2111655]. In mammals, MCH is predominantly expressed in the hypothalamus, and functions as a neurotransmitter in the control of a range of functions [PMID: 2111655]. A major role of MCH is thought to be in the regulation of feeding: injection of MCH into rat brains stimulates feeding; expression of MCH is upregulated in the hypothalamus of obese and fasting mice; and mice lacking MCH are lean and eat less [PMID: 8170923]. MCH and alpha melanocyte-stimulating hormone (alpha-MSH) have antagonistic effects on a number of physiological functions. Alpha-MSH darkens pigmentation in fish and reduces feeding in mammals, whereas MCH increases feeding [PMID: 8170923, PMID: 2111655].

An orphan GPCR, previously known as SLC-1, has been identified as a receptor for MCH [PMID: 8170923]. Expression of the receptor has been found at highest levels in the brain, with moderate levels in the eye and skeletal muscle, and lower levels in the tongue and pituitary. In the brain, the receptor is expressed extensively in the hippocampus, olfactory regions and medial nucleus accumbens, a distribution that corresponds to connections between MCH-containing neurons and areas of the brain involved in taste and olfaction [PMID: 2111655]. This supports a role for the MCH receptor in olfactory learning and reinforcement mechanisms. The receptor is also found in parts of the hypothalamus, such as the ventromedial nucleus, that are known to regulate feeding and metabolism. The MCH receptor is expressed at moderate levels in the substantia nigra, ventral tegmental area and amygdala, suggesting that MCH may modulate the dopaminergic system. Expression has also been found in the locus coeruleus, indicating a possible role in the control of noradrenaline responses, including vigilance, attention, memory and sleep. Binding of MCH to the receptor results in inhibition of forskolin-stimulated cyclic AMP accumulation in a pertussis toxin sensitive manner, release of intracellular calcium in a partially pertussis toxin sensitive manner and activation of MAP kinase in a partially protein kinase C dependent manner [PMID: 2830256]. This indicates that the MCH receptor is capable of coupling to G proteins of the Gi, Go and Gq classes.

GO terms

Biological Process

GO:0007218 neuropeptide signaling pathway

Molecular Function

GO:0030273 melanin-concentrating hormone receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PRINTS