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Melanocyte-stimulating Hormone (melanocyte-stimulating + hormone)
Selected AbstractsAntioxidant and anti-inflammatory activities of melanocortin peptidesEXPERIMENTAL DERMATOLOGY, Issue 9 2004J. W. Haycock ,-Melanocyte-stimulating hormone (,-MSH) has previously been identified as a potent anti-inflammatory agent in various tissues including the skin. It operates by binding to the melanocortin-1 receptor (MC-1R) which results in the elevation of cyclic AMP. ,-MSH opposes the action of several proinflammatory cytokines including tumour necrosis factor-, (TNF-,). We have shown that ,-MSH can inhibit TNF-,-stimulated activation of nuclear factor-,B (NF-,B) in human cultured melanocytes, melanoma cells, keratinocytes, fibroblasts, Schwann cells and olfactory ensheathing cells. It also inhibits TNF-,-stimulated upregulation of intercellular adhesion molecule-1 (ICAM-1) in many of these cells and can inhibit peroxide-stimulated activation of glutathione peroxidase, suggesting an antioxidant role. ,-MSH is also able to stimulate intracellular calcium release in keratinocytes and fibroblasts (which do not readily show detectible cyclic AMP elevation) but only in the presence of PIA (an adenosine agonist). The carboxyl terminal tripeptides KPV/KP-D-V are reported to be the minimal sequences necessary to convey anti-inflammatory potential, but evidence on how they act is not fully known. Stable transfection of Chinese hamster ovary cells with MC-1R suggests that the KPV peptides operate by this receptor, at least by elevating intracellular calcium. Elevation of cyclic AMP by these tripeptides has not been detected in any cell type studied; however, calcium elevation can inhibit TNF-,-stimulated NF-,B activity (as for cyclic AMP). In conclusion, the MSH peptides convey anti-inflammatory and antioxidant activity in many cell types in skin and nerve, by counteracting proinflammatory cytokine signalling. The KPV peptides appear to act functionally via the MC-1R and can also elevate intracellular calcium. [source] Neuropeptides and appetite controlDIABETIC MEDICINE, Issue 8 2002J. P. H. Wilding Abstract Obesity is important in the aetiology of type 2 diabetes, and presents a major barrier to its successful prevention and management. Obesity develops when energy intake exceeds energy expenditure over time. A complex system has evolved to maintain energy homeostasis, but this is biased towards weight gain. Meal size is controlled by a series of short-term hormonal and neural signals that derive from the gastrointestinal tract, such as cholecystokinin whereas others may initiate meals, such as the recently discovered hormone, ghrelin. Other hormones such as insulin and leptin, together with circulating nutrients, indicate long-term energy stores. All these signals act at several central nervous system (CNS) sites but the pathways converge on the hypothalamus, which contains a large number of peptide and other neurotransmitters that influence food intake. As energy deficit is most likely to compromise survival, it is not surprising that the most powerful of these pathways are those that increase food intake and decrease energy expenditure when stores are depleted. When energy stores are low, production of leptin from adipose tissue, and thus circulating leptin concentrations fall, leading to increased production of hypothalamic neurotransmitters that strongly increase food intake, such as neuropeptide Y (NPY), galanin and agouti-related protein (AGRP) and decreased levels of ,-melanocyte-stimulating hormone (,-MSH), cocaine and amphetamine-regulated transcript (CART) and neurotensin that reduce food intake and increase energy expenditure. The finding that mutations in leptin and POMC lead to severe early onset obesity in bumans has highlighted the importance of these peptides in humans. This new understanding may eventually lead to new treatments for obesity that will be of particular benefit in the prevention and treatment of type 2 diabetes. Diabet. Med. 19, 619,627 (2002) [source] Prostaglandin D2 production in FM55 melanoma cells is regulated by ,-melanocyte-stimulating hormone and is not related to melanin productionEXPERIMENTAL DERMATOLOGY, Issue 8 2010Mojgan Masoodi Please cite this paper as: Prostaglandin D2 production in FM55 melanoma cells is regulated by ,-melanocyte-stimulating hormone and is not related to melanin production. Experimental Dermatology 2010; 19: 751,753. Abstract:, This study shows that prostaglandins in human FM55 melanoma cells and epidermal melanocytes are produced by COX-1. Prostaglandin production in FM55 melanoma cells was unrelated to that of melanin suggesting that the two processes can occur independently. ,-Melanocyte-stimulating hormone, which had no effect on melanin production in FM55 cells, stimulated PGD2 production in these cells without affecting PGE2. While cAMP pathways may be involved in regulating PGD2 production, our results suggest that ,-MSH acts independently of cAMP, possibly by regulating the activity of lipocalin-type PGD synthase. This ,-MSH-mediated effect may be associated with its role as an immune modulator. [source] Monitoring neuropeptide-specific proteases: processing of the proopiomelanocortin peptides adrenocorticotropin and , -melanocyte-stimulating hormone in the skinEXPERIMENTAL DERMATOLOGY, Issue 10 2006Simone König Abstract:, The neuroendocrine precursor protein proopiomelanocortin (POMC) and its derived neuropeptides are involved in a number of important regulatory processes in the central nervous system as well as in peripheral tissues. Despite its important role in controlling the local activation of melanocortin (MC) receptors, the extracellular proteolytic processing of POMC peptides has received little attention. The mechanisms relevant for controlling the bioavailability of adrenocorticotropin and melanocyte-stimulating hormones for the corresponding MC receptors in the skin by specific peptidases such as neprilysin (neutral endopeptidase; NEP) or angiotensin-converting enzyme (ACE) have been addressed in a number of recent investigations. This review summarizes the current body of knowledge concerning the qualitative and quantitative POMC peptide processing with respect to the action and specificity of NEP and ACE and discusses relevant recent analytical methodologies. [source] Immunoreactivity of corticotropin-releasing hormone, adrenocorticotropic hormone and , -melanocyte-stimulating hormone in alopecia areataEXPERIMENTAL DERMATOLOGY, Issue 7 2006Hei Sung Kim Abstract:, Psychological factors are believed to play a role in the pathogenesis of alopecia areata (AA), a frequently encountered hair disorder. In our study, statistically significant elevation of psychological stress was felt by AA patients prior hair loss compared with control, which was strongly believed contributory to hair loss (t -test, P < 0.01). The corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) mRNA have been identified in the basal layer of the epidermis and pilosebaceous units of the normal scalp. And with the recent discovery of melanocytes and dermal fibroblasts capable of corticosterone production, the presence of a local stress response system resembling the hypothalamic,pituitary,adrenal (HPA) axis has been suggested. The local stress response system is involved in regulation of the normal hair cycle, but its precise role in AA is unknown. The influence of a local HPA axis or rather, CRH,POMC axis in AA was investigated by analysing immunohistochemically the expression levels of CRH and POMC peptides, including the adrenocorticotropic hormone (ACTH) and , -melanocyte-stimulating hormone (, -MSH), in a number of AA lesions and normal scalp (as control). The epidermis and pilosebaceous units of normal scalp stained weakly with CRH, ACTH and , -MSH, whereas those from the affected sites of the AA group showed intense expression of the peptides (chi-square test, P < 0.01). The meaning of this enhanced expression and their role in the pathogenesis of AA should be further evaluated in future. [source] Identification of novel genes regulated by ,-melanocyte-stimulating hormone in murine bone marrow-derived dendritic cellsEXPERIMENTAL DERMATOLOGY, Issue 9 2004T. Brzoska Many strains of evidence indicate that ,-melanocyte-stimulating hormone (,-MSH) elicits its immunomodulatory activity via binding to melanocortin receptors (MC-Rs) expressed on monocytes and dendritic cells. In order to identify novel target genes regulated by ,-MSH in these cells, we prepared bone marrow-derived dendritic cell precursors from BALB/c mice and treated them with GM-CSF and IL-4 for 6 days. The MC-R profile on these immature dendritic cells was first determined by quantitative RT-PCR. Both transcripts for MC-1R and MC-5R were detected in these cells. Cells were subsequently stimulated with dinitrobenzene sulfonic acid (DNBS), ,-MSH or both substances for 2 or 16 h. After RNA preparation, cDNA synthesis and in vitro transcripton hybridization of biotinylated cRNA samples was performed on MG U74A Affymetrix gene chips. Data evaluation, cleansing, extraction and analysis of the more than 12 000 cloned genes and expressed sequence tags were performed using the GENE DATA ANALYST vs. 1 Expressionist software. Filter criteria included a minimum threshold of 100, normalization by the logarithmic mean and a quality setting of P < 0.04. Changes with a change factor of >2 were regarded as significant. As expected, stimulation with DNBS resulted in induction or upregulation of genes encoding proinflammatory cytokines, growth factors, signal transduction intermediates and transcription factors. Treatment with ,-MSH blocked the DNBS-driven upregulation of several known genes such as IL-1 or CD86. On the other hand, ,-MSH modulated the expression of several novel genes implicated in immunomodulation, e.g. IL-1, converting enzyme, IFN-, receptor, FK506-binding proteins or several neuropeptides and their receptors. These data indicate novel molecular targets by which ,-MSH exerts its immunomodulatory activities in immunocompetent cells. [source] Loss-of-function variants of the human melanocortin-1 receptor gene in melanoma cells define structural determinants of receptor functionFEBS JOURNAL, Issue 24 2002Jesús Sánchez Más The ,-melanocyte-stimulating hormone (,MSH) receptor (MC1R) is a major determinant of mammalian skin and hair pigmentation. Binding of ,MSH to MC1R in human melanocytes stimulates cell proliferation and synthesis of photoprotective eumelanin pigments. Certain MC1R alleles have been associated with increased risk of melanoma. This can be theoretically considered on two grounds. First, gain-of-function mutations may stimulate proliferation, thus promoting dysplastic lesions. Second, and opposite, loss-of-function mutations may decrease eumelanin contents, and impair protection against the carcinogenic effects of UV light, thus predisposing to skin cancers. To test these possibilities, we sequenced the MC1R gene from seven human melanoma cell (HMC) lines and three giant congenital nevus cell (GCNC) cultures. Four HMC lines and two GCNC cultures contained MC1R allelic variants. These were the known loss-of-function Arg142His and Arg151Cys alleles and a new variant, Leu93Arg. Moreover, impaired response to a superpotent ,MSH analog was demonstrated for the cell line carrying the Leu93Arg allele and for a HMC line homozygous for wild-type MC1R. Functional analysis in heterologous cells stably or transiently expressing this variant demonstrated that Leu93Arg is a loss-of-function mutation abolishing agonist binding. These results, together with site-directed mutagenesis of the vicinal Glu94, demonstrate that the MC1R second transmembrane fragment is critical for agonist binding and maintenance of a resting conformation, whereas the second intracellular loop is essential for coupling to the cAMP system. Therefore, loss-of-function, but not activating MC1R mutations are common in HMC. Their study provides important clues to understand MC1R structure-function relationships. [source] Nociceptin/Orphanin FQ Peptide in Hypothalamic Neurones Associated with the Control of Feeding BehaviourJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2010N. Maolood Nociceptin/orphanin FQ (N/OFQ), an endogenous peptide agonist of the opioid N/OFQ receptor, has been implicated in the regulation of energy balance. In the present study, we have used immunohistochemistry to investigate the cellular localisation and colocalisation of N/OFQ-immunoreactive cell bodies in hypothalamic regions containing neurones producing orexigenic or anorexigenic transmitters. In colchicine-treated rats, N/OFQ immunoreactivity was demonstrated in many cell bodies of the arcuate nucleus (Arc), paraventricular nucleus (PVN) and lateral hypothalamic area (LHA). Double-labelling revealed that N/OFQ was present in some neurones located in the ventrolateral part of the Arc producing pro-opiomelanocortin, as shown by the presence of the anorexigenic peptides ,-melanocyte-stimulating hormone (,-MSH) and cocaine- and amphetamine-regulated transcript and, occasionally, in single neurones of the ventrolateral Arc producing orexigenic agouti-related peptide, but not neuropeptide Y. N/OFQ immunoreactivity was also demonstrated in a few tyrosine hydroxylase- or dynorphin (DYN)-containing neurones in the dorsomedial part of the Arc. In the parvocellular PVN, N/OFQ was demonstrated in some thyrotrophin-releasing hormone- or DYN-, but not corticotrophin-releasing hormone-containing neurones. Most N/OFQ-immunoreactive neurones in the LHA contained orexin- and DYN, but not melanin-concentrating hormone. The results obtained, demonstrating the presence of N/OFQ in some ,-MSH- and in many orexin-containing neurones, suggest a functional relationship between these neuropeptides and N/OFQ in the control of feeding behaviour and body weight. [source] Loss of Hypothalamic Response to Leptin During Pregnancy Associated with Development of Melanocortin ResistanceJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2009S. R. Ladyman Hypothalamic leptin resistance during pregnancy is an important adaptation that facilitates the state of positive energy balance required for fat deposition in preparation for lactation. Within the arcuate nucleus, pro-opiomelanocortin (POMC) neurones and neuropeptide Y (NPY)/agouti-related gene protein (AgRP) neurones are first-order leptin responsive neurones involved in the regulation of energy balance. The present study aimed to investigate whether the regulation of these neuropeptides is disrupted during pregnancy in association with the development of leptin resistance. As measured by quantitative in situ hybridisation, POMC and AgRP mRNA levels were not significantly different during pregnancy, whereas NPY mRNA levels increased such that, by day 21 of pregnancy, levels were significantly higher than in nonpregnant, animals. These data suggest that these neurones were not responding normally to the elevated leptin found during pregnancy. To further characterise the melanocortin system during pregnancy, double-label immunohistochemistry was used to quantify leptin-induced phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) in POMC neurones, using ,-melanocyte-stimulating hormone (MSH) as a marker. The percentage of ,-MSH neurones containing leptin-induced pSTAT3 did not significantly differ from nonpregnant animals, indicating that there was no change in the number of POMC neurones that respond to leptin during pregnancy. Treatment with ,-MSH significantly reduced food intake in nonpregnant rats, but not in pregnant rats, indicating resistance to the satiety actions of ,-MSH during pregnancy. The data suggest that multiple mechanisms contribute to leptin resistance during pregnancy. As well as a loss of responses in first-order leptin-responsive neurones in the arcuate nucleus, there is also a downstream disruption in the melanocortin system. [source] Effect of Intracerebroventricular Administration of the Octadecaneuropeptide on the Expression of Pro-Opiomelanocortin, Neuropeptide Y and Corticotropin-Releasing Hormone mRNAs in Rat HypothalamusJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2003V. Compčre Abstract Intracerebroventricular (i.c.v.) administration of the octadecaneuropeptide (diazepam-binding inhibitor [33,50]; ODN) exerts a potent anorexigenic effect in the rat. We studied the effect of ODN on three neuropeptides involved in feeding behaviour: the orexigenic peptide neuropeptide Y (NPY) and two anorexigenic peptides, corticotropin-releasing hormone (CRH) and the pro-opiomelanocortin (POMC)-derived peptide , -melanocyte-stimulating hormone. The effect of i.c.v. administration of ODN (0.1 µg/kg and 1 µg/kg) on mRNA expression of the peptides in male rat hypothalamus was evaluated by semiquantitative in situ hybridization. In the arcuate nucleus, NPY-expressing neurones were mostly found in the inner zone in close proximity of the third ventricle. ODN at the dose of 0.1 µg/kg induced a significant decrease of 17.4% in NPY mRNA expression, while the depressing effect was more marked (31.4%) with the highest dose of ODN (1 µg/kg). POMC-expressing neurones were more laterally located in the arcuate nucleus. Administration of ODN at 0.1 µg/kg and 1 µg/kg doses induced increases of 33.5% and 27.4% in POMC mRNA expression, respectively. Labelling obtained with the CRH cRNA probe was essentially distributed throughout the medial parvocellular area of the hypothalamic paraventricular nucleus. ODN, at doses of 0.1 and 1 µg/kg, resulted in 17.8% and 32.8% decreases in CRH mRNA expression, respectively. The present data suggest that ODN might exert its anorexigenic effect by increasing mRNA expression of POMC and decreasing mRNA expression of NPY in the arcuate nucleus. [source] Anorexic But Not Pyrogenic Actions of Interleukin-1 are Modulated by Central Melanocortin-3/4 Receptors in the RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2001C. B. Lawrence Abstract The cytokine interleukin-1 (IL-1), which mediates many responses to infection and injury, induces anorexia and fever through direct actions in the central nervous system. The melanocortin neuropeptides, such as alpha melanocyte-stimulating hormone (,-MSH), reportedly antagonize many actions of IL-1, including fever and anorexia. However, it is unknown whether endogenous melanocortins modulate anorexia induced by IL-1. The objective of the present study was to establish the effect of endogenous melanocortins on IL-1-induced anorexia and fever in the rat. Intracerebroventricular (i.c.v.) injection of IL-1, caused a significant reduction in food intake and body weight gain, and a rise in core body temperature in conscious rats. Coadministration of the melanocortin-3/4 receptor (MC3/4-R) antagonist, SHU9119, reversed IL-1,-induced reductions in food intake and body weight, but did not affect the febrile response to IL-1,. These data suggest IL-1, may elicit its effects on food intake through the melanocortin system, predominantly via the MC3-R or MC4-R. In contrast, IL-1,-induced fever does not appear to be mediated or modulated by MC3-R or MC4-R activity. [source] Effects of Melanogenesis-Inducing Nitric Oxide and Histamine on the Production of Eumelanin and Pheomelanin in Cultured Human MelanocytesPIGMENT CELL & MELANOMA RESEARCH, Issue 1 2003Michael W. Lassalle Melanin pigments produced in human melanocytes are classified into two categories; black coloured eumelanin and reddish-yellow pheomelanin. Stimulation of melanocytes with ,-melanocyte-stimulating hormone (,-MSH), one of several melanogenic factors, has been reported to enhance eumelanogenesis to a greater degree than pheomelanogenesis, which contributes to hyperpigmentation in skin. Nitric oxide (NO) and histamine are also melanogenesis-stimulating factors that are released from cells surrounding melanocytes following ultraviolet (UV) irradiation. In this study, the effects of NO and histamine on the ratio of eumelanin and pheomelanin were examined in human melanocytes, and then compared with that of ,-MSH. The amounts of eumelanin and pheomelanin were quantified using high-performance liquid chromatography analysis after oxidation and hydrolysis of melanin. Melanogenesis was induced by the addition of ,-MSH, NO, or histamine to melanocytes. The amount of eumelanin production significantly increased with independent stimulation by these melanogenic factors, especially histamine, while that of pheomelanin significantly increased with ,-MSH and NO, but only slightly with histamine. As a result, the ratio of eumelanin and pheomelanin increased significantly with the addition of NO or histamine. These results suggest that NO and histamine, as in the case of ,-MSH, may contribute to UV-induced hyperpigmentation by enhancing eumelanogenesis. [source] Oestrogenic Steroids and Melanoma Cell Interaction with Adjacent Skin Cells Influence Invasion of Melanoma Cells In VitroPIGMENT CELL & MELANOMA RESEARCH, Issue 2000SHEILA MAC NEIL The invasion of melanoma is complex and multi-staged and involves changes in both cell/extracellular matrix (ECM) and cell/cell interactions. Female steroids and ,-MSH have also been reported to influence metastatic melanoma progression, but their mechanisms of action are unknown. Accordingly, our aim was to establish in vitro models to examine (a) the influence of sex steroids and ,-melanocyte-stimulating hormone (,-MSH) on tumour invasion and the influence of (b) ECM proteins and (c) adjacent cells on melanoma invasion. In the first model, melanoma cell invasion through fibronectin over 20 hr under serum-free conditions was used to investigate the effects of 17,-oestradiol and oestrone on the invasion of human melanoma cell lines, A375-SM and HBL. A375-SM, but not HBL cells, proved very susceptible to inhibition by female steroids. However, invasion of the HBL line was inhibited by ,-MSH. Using the second model of reconstructed human skin based on de-epidermised acellular dermis, we found that the HBL cells on their own failed to invade into the dermis (irrespective of the presence or absence of the basement membrane). However, there was a significant synergistic interaction between keratinocytes, fibroblasts and HBL cells, such that a modest invasion of HBLs into the dermis was seen within 2 weeks when other skin cells were present. In contrast, A375-SM cells showed a significant ability to invade the dermis in the absence of other cells, with less invasion when other skin cells were present. In summary, these models have provided new information on the extent to which melanoma cell invasion is sensitive to oestrogenic steroids and to ,-MSH and to interaction, not only with adjacent skin cells but also to the presence of basement membrane antigens. [source] Conserved neurochemical pathways involved in hypothalamic control of energy homeostasisTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2007Paul M. Forlano Abstract The melanocortin system, which includes ,-melanocyte-stimulating hormone (,-MSH) and its endogenous antagonist, agouti-related protein (AgRP), is fundamental for the central control of energy homeostasis in mammals. Recent studies have demonstrated that many neuropeptides involved in the control of ingestive behavior and energy expenditure, including melanocortins, are also expressed and functional in teleost fishes. To test the hypothesis that the underlying neural pathways involved in energy homeostasis are conserved throughout vertebrate evolution, the neuroanatomical distribution of ,-MSH in relation to AgRP was mapped in a teleost (zebrafish, Danio rerio) by double-label immunocytochemistry. Zebrafish ,-MSH- and AgRP-immunoreactive (ir) cells are found in discrete populations in the ventral periventricular hypothalamus, the proposed arcuate homologue in teleosts. Major ascending projections are similar for both peptides, and dense ir-fibers innervate preoptic and ventral telencephalic nuclei homologous to paraventricular, lateral septal, and amygdala nuclei in mammals. Furthermore, ,-MSH and AgRP-ir somata and fibers are pronounced at 5 days post fertilization when yolk reserves are depleted and larvae begin to feed actively, which supports the functional significance of these peptides for feeding behavior. The conservation of melanocortin peptide function and projection pathways further support zebrafish as an excellent genetic model system to investigate basic mechanisms involved in the central regulation of energy homeostasis. J. Comp. Neurol. 505:235,248, 2007. © 2007 Wiley-Liss, Inc. [source] How Palatable Food Disrupts Appetite RegulationBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2005Charlotte Erlanson-Albertsson Hunger signals may be generated in peripheral organs (e.g. ghrelin) but most of them are expressed in the hypothalamus (neuropeptide Y, orexins, agouti-related peptide, melanin concentrating hormone, endogenous opiates and dopamine) and are expressed during situations of energy deficiency. Some satiety signals, such as cholecystokinin, glucagon-like peptide 1, peptide YY and enterostatin are released from the digestive tract in response to food intake. Others, such as leptin and insulin, are mobilized in response to perturbations in the nutritional state. Still others are generated in neurones of the hypothalamus (,-melanocyte-stimulating hormone and serotonin). Satiety signals act by inhibiting the expression of hunger signals and/or by blunting their effect. Palatable food, i.e. food rich in fat and sugar, up-regulates the expression of hunger signals and satiety signals, at the same time blunting the response to satiety signals and activating the reward system. Hence, palatable food offsets normal appetite regulation, which may explain the increasing problem of obesity worldwide. [source] Alterations in the epidermal,dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skinBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2006N. Ünver Summary Background, Senile lentigo (SL) is a pigmentation disorder that occurs predominantly on the dorsa of the hands, the forearms and the face; its incidence increases with age. Histological hallmarks of SL lesions are hyperpigmentation of the epidermis and elongation of the epidermal rete ridges. Various factors such as , -melanocyte-stimulating hormone, endothelin-1 or stem cell factor are involved in the onset and maintenance of the increased pigmentation. Alterations of the dermal compartment have not yet been analysed in detail in SL. Objectives, To study the occurrence and distribution of melanin in the dermis from SL and aged skin, biopsies from 12 subjects were morphologically analysed by light and electron microscopy in comparison with unaffected skin. Methods, Punch biopsies of SL and adjacent skin from 12 male or female volunteers aged 52,81 years were prepared for light and electron microscopy and samples were analysed by morphological, morphometric, histochemical and immunohistochemical methods. Results, The epidermis from SL revealed morphological features such as hyperpigmentation of basal keratinocytes and the formation of elongated rete ridges. S100+ melanocytes in the stratum basale were not markedly increased, indicating that the hyperpigmentation is predominantly due to changes in melanin synthesis, distribution or turnover. Quantification of epidermal cells expressing the proliferation marker Ki67 did not show an increase of this parameter in SL, indicating that at least in the established lesion cell proliferation is not enhanced. We further focused on the dermal compartment and observed granulated cells which were more abundant in SL. Electron microscopic and histochemical analysis revealed that the granulation of these cells is based on melanosomes, mostly present in large melanosomal complexes. Immunohistochemistry using antibodies to CD68 and factor XIIIa (FXIIIa) showed these melanophages to be predominantly FXIIIa+ dermal dendrocytes, which were about six times more abundant than CD68+ macrophages. Conclusions, In SL an increased number of melanophages was found compared with unaffected skin from the same subject. These melanophages were identified as FXIIIa+ dermal dendrocytes. Possible functional consequences of the massive melanin uptake by dermal dendrocytes are discussed. [source] Relevance of the C-terminal Arg-Phe sequence in ,2 -melanocyte-stimulating hormone (,2 -MSH) for inducing cardiovascular effects in conscious ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2000M J M A Nijsen The cardiovascular effects by ,2 -melanocyte-stimulating hormone (,2 -MSH) are probably not due to any of the well-known melanocortin subtype receptors. We hypothesize that the receptor for Phe-Met-Arg-Phe-amide (FMRFa) or Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-amide (neuropeptide FF; NPFFa), other Arg-Phe containing peptides, is the candidate receptor. Therefore, we studied various Arg-Phe containing peptides to compare their haemodynamic profile with that of ,2 -MSH(6,12), the most potent fragment of ,2 -MSH. Mean arterial pressure (MAP) and heart rate (HR) changes were measured in conscious rats after intravenous administration of ,2 -MSH related peptides. Phe-Arg-Trp-Asp-Arg-Phe-Gly (,2 -MSH(6,12)), FMRFa, NPFFa, Met-enkephalin-Arg-Phe-amide (MERFa), Arg-Phe-amide (RFa), acetyl-Phe-norLeu-Arg-Phe-amide (acFnLRFa) and desamino-Tyr-Phe-norLeu-Arg-Phe-amide (daYFnLRFa) caused a dose-dependent increase in MAP and HR. ,2 -MSH(6,12) showed the most potent cardiovascular effects (ED50=12 nmol kg,1 for ,MAP; 7 nmol kg,1 for ,HR), as compared to the other Arg-Phe containing peptides (ED50=177,292 nmol kg,1 for ,MAP; 130,260 nmol kg,1 for ,HR). Peptides, which lack the C-terminal Arg-Phe sequence (Lys-Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Pro-Gly (,2 -pro11 -MSH), desamino-Tyr-Phe-norLeu-Arg-[L-1,2,3,4 tetrahydroisoquinoline-3-carboxylic acid]-amide (daYFnLR[TIC]a) and Met-enkephalin (ME)), were devoid of cardiovascular actions. The results indicate that the baroreceptor reflex-mediated reduction of tonic sympathetic activity due to pressor effects is inhibited by ,2 -MSH(6,12) and that its cardiovascular effects are dependent on the presence of a C-terminal Arg-Phe sequence. It is suggested that the FMRFa/NPFFa receptor is the likely candidate receptor, involved in these cardiovascular effects. British Journal of Pharmacology (2000) 131, 1468,1474; doi:10.1038/sj.bjp.0703709 [source] | |||||||||||||||||||||||||