New aspects on the melanocortins and their receptors

Wikberg, Jarl E. S.; Muceniece, Ruta; Mandrika, Ilona; Prūsis, Peteris; Lindblom, Jessica; Post, Claes; Skottner, A.

doi:10.1006/phrs.2000.0725

Cited by 302 publications

(295 citation statements)

References 241 publications

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“…Melanocortin-1 receptor DNA sequencing showed that the HBL line expressed wild-type MC-1R, whereas the A375-SM and C8161 lines were homozygous and heterozygous for Arg151Cys, respectively. This polymorphism is known to convey a loss of function on receptor coupling to cAMP (reviewed in Wikberg et al, 2000). The heterozygous expression of Arg151Cys would suggest a potential for signalling; however, partially functional responses in the A375-SM line (homozygous Arg151Cys) would suggest either that this polymorphism conveys some function (as opposed to total loss) or that a signal other than cAMP is conveyed from the receptor in a region outside of the Arg151Cys site.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

et al. 2003

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a-Melanocyte stimulating hormone (a-MSH) is known to have pleiotrophic functions including pigmentary, anti-inflammatory, antipyretic and immunoregulatory roles in the mammalian body. It is also reported to influence melanoma invasion with levels of a-, b-and g-MSH correlated clinically with malignant melanoma development, but other studies suggest a-MSH acts to retard invasion. In the present study, we investigated the action of a-MSH on three human melanoma cell lines (HBL, A375-SM and C8161) differing in metastatic potential. a-melanocyte-simulating hormone reduced invasion through fibronectin and also through a human reconstructed skin composite model for the HBL line, and inhibited proinflammatory cytokine-stimulated activation of the NF-kB transcription factor. However, A375-SM and C8161 cells did not respond to a-MSH. Immunofluorescent microscopy and Western blotting identified melanocortin-1 receptor (MC-1R) expression for all three lines and MC-2R on HBL and A375-SM lines. Receptor binding identified a similar affinity for a-MSH for all three lines with the highest number of binding sites on HBL cells. Only the HBL melanoma line demonstrated a detectable cyclic adenosine monophosphate (cAMP) response to a-MSH, although all three lines responded to acute a-MSH addition ( þ (À)-N 6 -(2-phenylisopropyl)-adenosine (PIA)) with an elevation in intracellular calcium. The nonresponsive lines displayed MC-1R polymorphisms (C8161, Arg (wt) 151/Cys 151; A375-SM, homozygous Cys 151), whereas the HBL line was wild type. Stable transfection of the C8161 line with wild-type MC-1R produced cells whose invasion was significantly inhibited by a-MSH. From this data, we conclude that a-MSH can reduce melanoma cell invasion and protect cells against proinflammatory cytokine attack in cells with the wild-type receptor (HBL).

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Section: Discussionmentioning

confidence: 99%

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

et al. 2003

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“…α-melanocortin stimulating hormone, α-MSH) are derived from a larger precursor molecule called the pro-opiomelanocortin (POMC) gene [9,10] and exert their biological effect via activation of a sub-group of G-protein coupled receptor, termed melanocortin receptors (MCR). To date five MCRs have been identified and they are all positively coupled to adenylate cyclase, signaling via protein kinase with agonism at these receptors leading to increases in intracellular cAMP [11]. Melanocortin peptides have long been reported to possess antiinflammatory effects in many experimental models of acute [12][13][14] and chronic inflammation, including inflammatory bowel disease [15], joint arthritis [16,17] and activation and consequent cytokine synthesis within the first few hours of treatment [20,21] and at later time points (>8h) induce the anti-inflammatory protein hemeoxygenase 1 [22] and IL-10 [24].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

A role for MC3R in modulating lung inflammation

Getting¹,

Riffo‐Vasquez²,

Pitchford³

et al. 2008

Pulmonary Pharmacology & Therapeutics

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“…30 Increases in erection frequencies were seen by injecting both ACTH and a-MSH directly into PVN of the hypothalamus. Blocking the MC4R with HS014, a non-selective MC4R antagonist, did not alter these responses.…”

Section: Melanocortins and Erectionmentioning

confidence: 99%

Preclinical effects of melanocortins in male sexual dysfunction

Shadiack¹,

Althof²

2008

Int J Impot Res

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The neurobiology of sexual behavior involves the interrelationships between sex steroids and neurotransmitters that result in both central nervous system (CNS) effects and effects in the genitalia. Tools such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scanning can help determine what areas of the brain are activated under sexual stimulation. Our understanding of the role of various neurotransmitters, neurosteroids and other CNS-acting compounds is improving. The role of CNS-acting compounds such as dopamine agonists in the treatment of male sexual dysfunction is under active investigation. Melanocortins have CNS and peripheral roles in a wide variety of bodily functions. The melanocortin agonist bremelanotide appears to act in the CNS to promote erections in preclinical models, and may also stimulate behaviors that facilitate sexual activity beyond their erectogenic effects.

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New aspects on the melanocortins and their receptors

Cited by 302 publications

References 241 publications

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

A role for MC3R in modulating lung inflammation

Preclinical effects of melanocortins in male sexual dysfunction

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