Melanocortin 4 receptor

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. We use the term clan 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 []. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The rhodopsin-like GPCRs themselves 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 [].

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. We use the term clan 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 []. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The nematode Caenorhabditis elegans has only 14 types of chemosensory neuron, yet is able to sense and respond to several hundred different chemicals because each neuron detects several stimuli []. Chemoperception is one of the central senses of soil nematodes like C. elegans which are otherwise 'blind' and 'deaf' []. Chemoreception in C. elegans is mediated by members of the seven-transmembrane G-protein-coupled receptor class (7TM GPCRs). More than 1300 potential chemoreceptor genes have been identified in C. elegans, which are generally prefixed sr for serpentine receptor. The receptor superfamilies include Sra (Sra, Srb, Srab, Sre), Str (Srh, Str, Sri, Srd, Srj, Srm, Srn) and Srg (Srx, Srt, Srg, Sru, Srv, Srxa), as well as the families Srw, Srz, Srbc, Srsx and Srr []. Many of these proteins have homologues in Caenorhabditis briggsae.

This entry represents serpentine receptor class sx (Srsx), which is a solo family amongst the superfamilies of chemoreceptors. Chemoperception is one of the central senses of soil nematodes like C. elegans which are otherwise 'blind' and 'deaf' [].

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. We use the term clan 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 []. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The rhodopsin-like GPCRs themselves 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 [].

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. We use the term clan 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 []. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The rhodopsin-like GPCRs themselves 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 [].

Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) and beta-endorphin are peptide products of pituitary pro-opiomelanocortin. ACTH regulates synthesis and release of glucocorticoids and aldosterone in the adrenal cortex; it also has a trophic action on these cells. ACTH and beta-endorphin are synthesised and released in response to corticotrophin-releasing factor at times of stress (heat, cold, infections, etc.) - their release leads to increased metabolism and analgesia. MSH has a trophic action on melanocytes, and regulates pigment production in fish and amphibia. The ACTH receptor is found in high levels in the adrenal cortex - binding sites are present in lower levels in the CNS. The MSH receptor is expressed in high levels in melanocytes, melanomas and their derived cell lines. Receptors are found in low levels in the CNS. MSH regulates temperature control in the septal region of the brain and releases prolactin from the pituitary.

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. We use the term clan 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 []. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The rhodopsin-like GPCRs themselves 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 [].

The ability of marijuana to activate the cannabinoid receptor provides a molecular explanation for its psychoactive effects and other CNS actions (which include hallucinations, memory deficits, altered time and space perception, CNS depression and appetite stimulation). The endogenous ligand at the cannabinoid receptor is unknown, although it may be a derivative of arachidonic acid. The cannabinoid receptor is widespread throughout the CNS, high levels occurring in the dendate gyrus, hippocampus and cerebral cortex, with more moderate levels in the hypothalamus and amygdala. It is also present in various cell lines, and in the periphery it is found in the testis and vas deferens.

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. We use the term clan 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 []. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The rhodopsin-like GPCRs themselves 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 [].

Melanocyte-stimulating hormones (MSH), adrenocorticotrophin (ACTH) and beta-endorphin are peptide products of pituitary pro-opiomelanocortin. MSH has a trophic action on melanocytes, and regulates pigment production in fish and amphibia. The MSH receptor is expressed in high levels in melanocytes, melanomas and their derived cell lines. Receptors are found in low levels in the CNS. MSH regulates temperature control in the septal region of the brain and releases prolactin from the pituitary.

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. We use the term clan 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 []. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The rhodopsin-like GPCRs themselves 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 [].

Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) and beta-endorphin are peptide products of pituitary pro-opiomelanocortin. ACTH regulates synthesis and release of glucocorticoids and aldosterone in the adrenal cortex; it also has a trophic action on these cells. ACTH and beta-endorphin are synthesised and released in response to corticotrophin-releasing factor at times of stress (heat, cold, infections, etc.) - their release leads to increased metabolism and analgesia. MSH has a trophic action on melanocytes, and regulates pigment production in fish and amphibia. The ACTH receptor is found in high levels in the adrenal cortex - binding sites are present in lower levels in the CNS. The MSH receptor is expressed in high levels in melanocytes, melanomas and their derived cell lines. Receptors are found in low levels in the CNS. MSH regulates temperature control in the septal region of the brain and releases prolactin from the pituitary.

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. We use the term clan 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 []. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The rhodopsin-like GPCRs themselves 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 [].

Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) and beta-endorphin are peptide products of pituitary pro-opiomelanocortin. ACTH regulates synthesis and release of glucocorticoids and aldosterone in the adrenal cortex; it also has a trophic action on these cells. ACTH and beta-endorphin are synthesised and released in response to corticotrophin-releasing factor at times of stress (heat, cold, infections, etc.) - their release leads to increased metabolism and analgesia. MSH has a trophic action on melanocytes, and regulates pigment production in fish and amphibia. The ACTH receptor is found in high levels in the adrenal cortex - binding sites are present in lower levels in the CNS. The MSH receptor is expressed in high levels in melanocytes, melanomas and their derived cell lines. Receptors are found in low levels in the CNS. MSH regulates temperature control in the septal region of the brain and releases prolactin from the pituitary.

A further gene, which encodes a melanocortin receptor that is functionally distinct from the ACTH and MSH receptors, has also been characterised []. The protein contains ~300 amino acids, with calculated molecular mass of ~36 kDa, and potential N-linked glycosylation and phosphorylation sites []. The melanocortin 5 receptor (MC5-R) mediates increase in cAMP accumulation with a characteristic pharmacology []. Very low expression levels have been detected in brain, while high levels are found in adrenals, stomach, lung and spleen []. In situ hybridisation studies have also shown the MC5 receptor to be expressed in the three layers of the adrenal cortex, predominantly in the aldosterone-producing zona glomerulosa cells []. Structure-activity studies have indicated that N- and C-terminal portions of alpha-MSH appear to be key determinants in the activation of mouse MC5R, while the melanocortin core heptapeptide sequence is devoid of pharmacological activity [].

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. We use the term clan 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 []. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The rhodopsin-like GPCRs themselves 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 [].

Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) and beta-endorphin are peptide products of pituitary pro-opiomelanocortin. ACTH regulates synthesis and release of glucocorticoids and aldosterone in the adrenal cortex; it also has a trophic action on these cells. ACTH and beta-endorphin are synthesised and released in response to corticotrophin-releasing factor at times of stress (heat, cold, infections, etc.) - their release leads to increased metabolism and analgesia. MSH has a trophic action on melanocytes, and regulates pigment production in fish and amphibia. The ACTH receptor is found in high levels in the adrenal cortex - binding sites are present in lower levels in the CNS. The MSH receptor is expressed in high levels in melanocytes, melanomas and their derived cell lines. Receptors are found in low levels in the CNS. MSH regulates temperature control in the septal region of the brain and releases prolactin from the pituitary.

A further gene, which encodes a melanocortin receptor that is functionally distinct from the ACTH and MSH receptors, has also been characterised []. The protein contains ~300 amino acids, with calculated molecular mass of ~36 kDa, and potential N-linked glycosylation and phosphorylation sites []. The melanocortin 4 receptor (MC4-R) is regulated by opiate administration []. Rat MC4-R is 95% identical to human MC4-R, and the potency of melanocortin peptides to stimulate cAMP production is similar in these two species homologues []. Expression of MC4-R mRNA was found to be enriched in the striatum, nucleus accumbens, and periaque-ductal gray, all of which are regions implicated in the behavioral effects of opiates (and are regions in which MC1-, MC3- and MC5-R are expressed at low or undetectable levels) []. MC4-R mRNA has been found in multiple sites in virtually every brain region, including the cortex, thalamus, hypothalamus, brainstem, and spinal cord []. Unlike the MC3-R, MC4-R mRNA is found in both parvicellular and magnocellular neurons of the paraventricular nucleus of the hypothalamus, suggesting a role in the central control of pituitary function [].