The Melanocortin-1 Receptor

Schaffer, Julie V.; Bolognia, Jean L.

doi:10.1001/archderm.137.11.1477

Cited by 131 publications

(69 citation statements)

References 70 publications

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“…Notably, BRAF, mutated in the majority of human melanomas, may represent a key relay point for signals regulating both melanocyte growth and differentiation. See the text for detail in the human population (Box et al, 1997;Smith et al, 1998;Chakraborty et al, 1999;Healy et al, 2000;Schaffer and Bolognia, 2001;Taylor, 2002). In fact, the MC1-R helps regulate multiple melanocytic activites (see below), and nonfunctional MC1-Rs have been linked with enhanced sensitivity to the cytotoxic effects of UV as well as an increased incidence of melanoma (Valverde et al, 1996;Palmer et al, 2000;Kennedy et al, 2001;Scott et al, 2002).…”

Section: Sunlight and The Damage It Causesmentioning

confidence: 99%

Ultraviolet radiation and cutaneous malignant melanoma

2003

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Recent years have seen a steady rise in the incidence of cutaneous malignant melanoma worldwide. Although it is now appreciated that the key to understanding the process by which melanocytes are transformed into malignant melanoma lies in the interplay between genetic factors and the ultraviolet (UV) spectrum of sunlight, the nature of this relation has remained obscure. Recently, prospects for elucidating the molecular mechanisms underlying such gene-environment interactions have brightened considerably through the development of UV-responsive experimental animal models of melanoma. Genetically engineered mice and human skin xenografts constitute novel platforms upon which to build studies designed to elucidate the pathogenesis of UV-induced melanomagenesis. The future refinement of these in vivo models should provide a wealth of information on the cellular and genetic targets of UV, the pathways responsible for the repair of UV-induced DNA damage, and the molecular interactions between melanocytes and other skin cells in response to UV. It is anticipated that exploitation of these model systems will contribute significantly toward the development of effective approaches to the prevention and treatment of melanoma.

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Section: Sunlight and The Damage It Causesmentioning

confidence: 99%

Ultraviolet radiation and cutaneous malignant melanoma

2003

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“…9 Neuropeptides, ACTH and α-MSH, are potent modulators of cognitive function and neurobehavioural activities in animals and humans. 10,11 The peptides consistently enhance selective attention and stimulus processing with a visual (but not an auditory) discrimination learning procedure.…”

Section: Discussionmentioning

confidence: 99%

“…MSH and ACTH equipotently act on melanocortin receptor-1 (MC1-R), initiating melanogenesis. 9 Of the allelic variants of the MC1-R gene identified in humans, three particular variants, Arg 151Cys, Arg160Trp, and Asp294His, are the most frequently encountered loss of function mutations. 20 These variants result in an increase in the pheomelanin/eumelanin ratio in the skin and hair, and are associated with red hair, fair skin, and poor tanning ability.…”

Section: Discussionmentioning

confidence: 99%

“…20 These variants result in an increase in the pheomelanin/eumelanin ratio in the skin and hair, and are associated with red hair, fair skin, and poor tanning ability. 9 The mechanisms controlling production of α-MSH have not been clarified, but most pituitary functions are controlled by negative feedback systems. End-organ failure (e.g., loss of function mutations) leads to an increase in the level of hormones.…”

Section: Discussionmentioning

confidence: 99%

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Midazolam causes less sedation in volunteers with red hair

Chua

Tsueda

Doufas

2004

Can J Anesth/J Can Anesth

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P Pu ur rp po os se e: : We studied sedation, cognition, and mood during midazolam infusion in volunteers with red and non-red (blond or brown) hair, to test the hypothesis that patients with red hair may require more drugs to attain desired levels of sedation.M Me et th ho od ds s: : Twenty red and 19 non-red hair subjects were studied in a randomized, placebo-controlled cross-over design. Subjects were studied during placebo and midazolam at 30 ng·mL -1 target effect site concentration. Sedation was assessed using the observer's assessment of alertness/sedation (OAA/S) scale, the drowsiness visual analogue scale (VAS), and the bispectral index; cognition was assessed using the Repeatable Battery for Assessment of Neuropsychological Status; and mood was assessed using the bipolar form of the Profile of Mood States (POMS).R Re es su ul lt ts s: : Red hair volunteers showed significantly higher OAA/S (P < 0.01) and lower drowsiness VAS (P < 0.05) scores compared to non-red hair subjects during midazolam infusion. Visuospatial score was significantly higher in subjects with red compared to nonred hair during placebo and midazolam trials. Delayed memory score was significantly higher during midazolam infusion in subjects with red compared to non-red hair. There were no group differences in POMS during either trials.C Co on nc cl lu us si io on n: : Midazolam appears to cause significantly less sedation and cognitive impairment in red haired subjects. Objectif : Étudier la sédation, la fonction cognitive et l'humeur pendant une perfusion de midazolam chez des volontaires aux cheveux roux et non roux (blonds ou châtains) pour tester l'hypothèse voulant que chez les patients aux cheveux roux, il faut de plus grandes quantités de médicaments pour obtenir les niveaux de sédation désirés. Méthode Conclusion : Le midazolam semble causer moins de sédation et d'altération de la fonction cognitive chez les sujets aux cheveux roux.NECDOTAL descriptions exist that subjects with red hair may faint easily and are difficult to anesthetize. 1 A mail survey of anesthesiologists A has shown that redhaired patients are perceived to have a propensity for drug hypersensitivity, airway difficulties, hemodynamic instability, dysrrhythmias, combativeness and confusion at anesthesia emergence, nausea/vomiting, and bleeding. Our clinical observations suggest that patients with red hair may also require more drugs to attain desired levels of sedation.

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“…The wild-type mouse has agouti coat color; the hair is banded where the tip has black eumelanin, the center has pheomelanin and the base again eumelanin. These bands of pigment are generated by pigment type switching, which is regulated primarily by the melanocortin-1 receptor (Mc1r) and its ligands, ␣-melanocyte-stimulating hormone (␣-MSH) and the agouti signal protein (ASP; reviewed by Schaffer andBolognia, 2001, Wolff, 2003;Garcia-Borron et al, 2005). These proteins are encoded by the extension (e, now Mc1r, also known as recessive yellow), pro-opiomelanocortin-1 (Pomc1), and agouti (a) coat color loci, respectively.…”

Section: Regulation Of Pigment Typementioning

confidence: 99%

Mouse coat color mutations: From fancy mice to functional genomics

Steingrı́msson

Copeland

Jenkins

2006

Developmental Dynamics

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Mouse coat color mutations have a long history in biomedical research. The viable and visible phenotype of most coat color mutations has made the pigment cell, the melanocyte, an ideal system for genetic, molecular, and cellular analysis. Molecular cloning and analysis of many of the different coat color mutations have revealed the roles of a diverse range of genes, and today we know more about the pathways and proteins that regulate the development and function of pigment cells than we know about most other cell types in mammalian organisms. Coat color mutations have also provided novel insights into stem cell biology and human diseases, including melanoma. In the future, it will be important to build on this history and knowledge by taking advantage of the extensive repertoire of recently developed genome-wide methodologies, available genomic information, and the powerful methods that have been developed for modifying the mouse genome to systematically dissect the development and function of this important cell type. The usefulness of coat color mutations has just begun to emerge. Developmental Dynamics 235: 2401-2411, 2006.

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The Melanocortin-1 Receptor

Cited by 131 publications

References 70 publications

Ultraviolet radiation and cutaneous malignant melanoma

Ultraviolet radiation and cutaneous malignant melanoma

Midazolam causes less sedation in volunteers with red hair

Mouse coat color mutations: From fancy mice to functional genomics

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