Disease relevance of Mc3r

• We conclude that the hypotension and bradycardia elicited by the release of alpha-MSH from arcuate neurons is mediated by neural melanocortin receptors (MC4-R/MC3-R) located in the DVC, whereas the similar effects of beta-endorphin, a peptide derived from the same precursor, are mediated by opiate receptors at the same site [1].
• We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat [2].
• 2. As was previously found by other investigators as well as by us gamma 2-MSH, a peptide suggested to be an agonist with selectivity for the melanocortin MC3 receptor, caused a dose-dependent, short lasting pressor response in combination with a tachycardia [3].

Psychiatry related information on Mc3r

• Rats were fasted overnight to promote feeding behavior, then injected intraperitoneally with LPS (100 micrograms/kg ip), followed 30 min later by intracerebroventricular injection of either alpha-MSH or the melanocortin receptor subtype 3/subtype 4 (MC3-R/MC4-R) antagonist SHU-9119 [4].

High impact information on Mc3r

• These findings, together with the detection of the MC3-R in all of these cell types, indicate a role for the melanocortin system in chondrogenesis [5].
• Expression of melanocortin-3 receptor messenger RNA in the brain was not altered in this hypoxic-ischaemic injury model and melanocortin-5 receptor messenger RNA was not detected in either control or hypoxic-ischaemic injured rat brains [6].
• Postnatal expression of melanocortin-3 receptor in rat diencephalon and mesencephalon [7].
• The results indicate that the effects of MSH peptides on female sexual behavior in this area are mediated through specific MC receptor, that could be the MC3 receptor and that NO mediates the melanocortins effects [8].
• Evidence that the effect of melanocortins on female sexual behavior in preoptic area is mediated by the MC3 receptor; Participation of nitric oxide [8].

Biological context of Mc3r

• Investigation of the melanocyte stimulating hormones on food intake. Lack Of evidence to support a role for the melanocortin-3-receptor [9].
• NPY is orexigenic and decreases energy expenditure whereas alpha-MSH reduces food consumption and stimulates catabolism. alpha-MSH is an endogenous ligand for the central melanocortin receptors, MC3-R and MC4-R [10].
• These studies therefore indicate a role for PKC isozymes in gamma-2-MSH/MC3-R receptor signaling and in neuronal cell differentiation [11].
• These data suggest that the physiological roles of neural melanocortin receptors, MC3R and MC4R, are likely determined by distinct tissue distribution patterns and suggest a role for hypothalamic and intra-adrenal melanocortin systems in the manifestation of stress related pathologies [12].
• These results indicate that reflex natriuresis after AUN is accompanied by an increase in plasma gamma-MSH but not ANP or oxytocin concentration and is prevented by intrarenal infusion of receptor antagonists with selectivity for MC3-R [13].

Anatomical context of Mc3r

• To identify the receptor type expressed during ontogeny, the developmental pattern of MC3-R and MC4-R mRNA was investigated by in situ hybridization in fetuses and offspring of time-pregnant Long Evans rats between E14 and postnatal day (P) 27 [14].
• To better understand the interplay between the AGRP and melanocortin signaling systems, we compared their nerve fiber distributions with each other by immunohistochemistry and their perikarya distribution with MC3R and MC4R by double in situ hybridization [15].
• Melanocortin-3 receptor mRNA expression in pro-opiomelanocortin neurones of the rat arcuate nucleus [16].
• In order to determine whether POMC neurones can modulate their own activity, we looked for the possible expression of the MC3-R gene in POMC-positive cell bodies in the rat hypothalamus [16].
• AGRP-containing neurons are not visualized in a number of areas, including portions of the amygdala, thalamus, and brain stem, that express MC3-R and MC4-R messenger RNA and receive innervation from POMC neurons that serve as the source of melanocortin agonists [17].

Associations of Mc3r with chemical compounds

• In addition, neither melanotan-II (1.0 nmol, a non-selective MC3/4-R agonist) nor gamma(1)-melanocyte-stimulating hormone (10 nmol, a selective MC3-R agonist) affected significantly GH release in fasted rats [18].
• 4. These results imply that the melanocortin-4-receptor, and not the melanocortin-3-receptor, is involved in the ACTH1-24-induced rise in plasma levels of ACTH and corticosterone, and excessive grooming [19].
• Detection of melanocortin-3 receptor mRNA in immature rat pituitary: functional relation to gamma3-MSH-induced changes in intracellular Ca2+ concentration [20]?
• Central MC3-R/MC4-R blockade did not affect Tb or food intake in the absence of LPS treatment, but it reversed the LPS-induced reduction in 24-h food intake and increased LPS-induced fever without altering the LPS-induced suppression of locomotion [4].

Regulatory relationships of Mc3r

• The proportion of POMC neurones expressing MC3-R mRNA was significantly higher in the most rostral (43.5%) than in the most posterior part of the arcuate nucleus (8.2%) [16].

Other interactions of Mc3r

• We investigated endogenous melanocortin ligand binding and activation at the MC3-R and MC4-R and their effects on feeding [9].
• RT-PCR of rat kidney RNA demonstrated reaction products of the expected size in both cortex and medulla for MC3-R, MC4-R, and MC5-R mRNA; no signal for MC1-R or MC2-R was detected [21].
• The occurrence of MC3-R mRNA in POMC-positive cell bodies was demonstrated using a double-labelling in situ hybridization technique [16].

Analytical, diagnostic and therapeutic context of Mc3r

• The effects of alpha-MSH are inhibited by microinjection to the same site of the novel MG4-R/MC3-R antagonist SHU9119 (2-100 pmol) but not naloxone (270 pmol), whereas the similar effects of intra-DVC injection of beta-endorphin (1 pmol) are inhibited by naloxone and not by SHU9119 [1].
• MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH [2].
• Finally, the melanocortin-3 receptor was detected in all examined cell types by Western blot [5].

References