Targeted deletion of melanocortin receptor subtypes 3 and 4, but not CART, alters nutrient partitioning and compromises behavioral and metabolic responses to leptin

2005 ◽  
Vol 19 (11) ◽  
pp. 1482-1491 ◽  
Author(s):  
Yubin Zhang ◽  
Gail E Kilroy ◽  
Tara M. Henagan ◽  
Vera Prpic‐Uhing ◽  
William G. Richards ◽  
...  
Keyword(s):  
Melanocortin Receptor ◽  
Metabolic Responses ◽  
Receptor Subtypes ◽  
Targeted Deletion ◽  
Nutrient Partitioning

Increased severity of renal impairment in nephritic mice lacking the EP1 receptor

2006 ◽  
Vol 84 (8-9) ◽  
pp. 877-885 ◽  
Author(s):  
Sherine Rahal ◽  
Lyne I. McVeigh ◽  
Yahua Zhang ◽  
Youfei Guan ◽  
Matthew D. Breyer ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Collecting Duct ◽  
Urine Osmolality ◽  
Permeability Barrier ◽  
Receptor Subtypes ◽  
Glomerular Permeability ◽  
Targeted Deletion ◽  
Matrix Expansion ◽  
Ep1 Receptor ◽  
Inflammatory Drugs

In experimental glomerulonephritis, inhibition of renal prostaglandin (PG) synthesis by nonsteroidal-anti-inflammatory drugs (NSAIDs) moderates proteinuria, yet can induce harmful effects on renal blood flow and Na+–K+–water balance thereby implicating 1 or more prostanoid receptor subtypes. We investigated the role of the PGE2 EP1 receptor in nephritis since it is expressed in the glomerulus, collecting duct and vasculature in which its activity might contribute to adaptive or maladaptive responses. Accordingly, a mouse model of accelerated antiglomerular basement membrane (anti-GBM) nephrotoxic serum (NTS) nephritis was induced in mice with targeted-deletion of the EP1 receptor (EP1−/−). Proteinuria was similar between wild-type (wt) and EP1−/− NTS groups, thus negating a role for this subtype in modulating the glomerular permeability barrier in this model of anti-GBM NTS. However, overall renal damage was more acute in NTS EP1−/− mice, as evidenced by the degree of glomerular mesangial matrix expansion and the frequency of tubular dilatations. These changes in renal pathology were accompanied by stronger impairment of renal function in NTS EP1−/− mice, such that levels of serum creatinine, urea, Na+, and K+ were each significantly higher than those observed in NTS wt mice. Lastly, compared with wt mice, induction of NTS more severely reduced urine osmolality and body mass in EP1−/− mice. Taken together, the increased renal impairment seen in NTS EP1−/− mice suggests that the EP1 subtype plays a compensatory role in the context of acute nephritis.

scholarly journals The Melanocortin System in Control of Inflammation

2010 ◽  
Vol 10 ◽  
pp. 1840-1853 ◽  
Author(s):  
Anna Catania ◽  
Caterina Lonati ◽  
Andrea Sordi ◽  
Andrea Carlin ◽  
Patrizia Leonardi ◽  
...  
Keyword(s):  
Receptor Activation ◽  
Brain Regions ◽  
New Drugs ◽  
Melanocortin Receptor ◽  
Receptor Subtypes ◽  
Melanocortin System ◽  
Inflammatory Disorders ◽  
Melanocyte Stimulating Hormone ◽  
Common Precursor ◽  
Anti Inflammatory

Melanocortin peptides, the collective term for α-, β-, and γ-melanocyte-stimulating hormone (α-, β-, γ-MSH) and adrenocorticotropic hormone (ACTH), are elements of an ancient modulatory system. Natural melanocortins derive from the common precursor pro-opiomelanocortin (POMC). Five receptor subtypes for melanocortins (MC1-MC5) are widely distributed in brain regions and in peripheral cells. Melanocortin receptor activation by natural or synthetic ligands exerts marked anti-inflammatory and immunomodulatory effects. The anticytokine action and the inhibitory influences on inflammatory cell migration make melanocortins potential new drugs for treatment of inflammatory disorders. Effectiveness in treatment of acute, chronic, and systemic inflammatory disorders is well documented in preclinical studies. Further, melanocortins are promising compounds in neuroprotection. This review examines the main signaling circuits in anti-inflammatory and immunomodulatory actions of melanocortins, and the potential therapeutic use of these molecules.

scholarly journals HIF-1 regulates hypoxia- and insulin-induced expression of apelin in adipocytes

2007 ◽  
Vol 293 (6) ◽  
pp. E1590-E1596 ◽  
Author(s):  
Alexander J. Glassford ◽  
Patrick Yue ◽  
Ahmad Y. Sheikh ◽  
Hyung J. Chun ◽  
Shirin Zarafshar ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Cobalt Chloride ◽  
Hypoxia Inducible Factor ◽  
Metabolic Responses ◽  
Quantitative Real Time Pcr ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Targeted Deletion ◽  
Hypoxia Inducible Factor 1

Apelin, a novel peptide with significant cardioactive properties, is upregulated by insulin in adipocytes. However, the mechanism by which insulin promotes apelin production is unknown. Hypoxia-inducible factor-1 (HIF-1), a heterodimeric transcription factor involved in the angiogenic and metabolic responses to tissue hypoxia, has been shown to be activated by insulin in various settings. We therefore hypothesized that HIF-1 regulates insulin-mediated apelin expression in adipocytes. 3T3-L1 cells were differentiated into adipocytes in culture. For experiments, serum-starved 3T3-L1 cells were exposed to insulin and/or a 1% O2 environment. Apelin expression was assessed using quantitative real-time PCR and ELISA. To directly assess the role of HIF-1 in apelin production, we differentiated mouse embryonic fibroblasts (MEFs) containing a targeted deletion of the HIF-1α gene into adipocytes and measured their response to insulin and hypoxia. Apelin expression in mature 3T3-L1 adipocytes was increased significantly by insulin and was attenuated by pharmacological inhibition of insulin signaling. Exposure of cells to either hypoxia or the chemical HIF activators cobalt chloride (CoCl2) and dimethyloxaloylglycine (DMOG) resulted in significant upregulation of apelin, consistent with a role for HIF in apelin induction. Moreover, hypoxia-, CoCl2-, DMOG-, and insulin-induced apelin expression were all attenuated in differentiated HIF-1α-deficient MEFs. In summary, in cultured 3T3-L1 adipocytes and differentiated MEFs, HIF-1 appears to be involved in hypoxia- and insulin-induced apelin expression.

scholarly journals The melanocortin receptor subtypes in chicken have high preference to ACTH-derived peptides

2004 ◽  
Vol 143 (5) ◽  
pp. 626-637 ◽  
Author(s):  
Maria K Ling ◽  
Eri Hotta ◽  
Zuzana Kilianova ◽  
Tatjana Haitina ◽  
Aneta Ringholm ◽  
...  
Keyword(s):  
Melanocortin Receptor ◽  
Receptor Subtypes ◽  
High Preference

Identification of melanocortin receptor subtypes involved in lipolysis in murine 3T3-L1 adipocytes

Appetite ◽  
2009 ◽  
Vol 52 (3) ◽  
pp. 849
Author(s):  
C. Møller ◽  
K. Raun ◽  
M.L. Jacobsen ◽  
B.S. Wulff
Keyword(s):  
Melanocortin Receptor ◽  
Receptor Subtypes

Abstract 374: Targeted Deletion of A 2B Adenosine Receptors Attenuates the Protective Effects of Myocardial Postconditioning

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Xinglin Tan ◽  
Stephen L Tilley ◽  
Thomas Krahn ◽  
Bunyen Teng ◽  
S. J Mustafa ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Troponin I ◽  
Diastolic Pressure ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Heart Weight ◽  
Receptor Subtypes ◽  
Protective Effects ◽  
Targeted Deletion ◽  
Beneficial Effects

Endogenous adenosine is an important ligand trigger for the cardioprotective effects of postconditioning (PostCon). To assess the hypothesis that A 2B adenosine receptor (A 2B AR) activation contributes to PostCon-induced protection, global ischemia-reperfusion was performed with and without PostCon or the selective A 2B agonist, BAY 60 – 6583 (BAY), in isolated wild-type (WT) and A 2B AR knockout (A 2B KO) mouse hearts. In WT hearts, PostCon improved post-ischemic recovery of left ventricular developed pressure (LVDP) to 63.3±1.6 % of pre-ischemic baseline vs. 49.9±1.6 % in non-PostCon controls (CTL), lowered end diastolic pressure (EDP) to 15.8±1.5 mmHg vs. 27.9±1.6 mmHg in CTL, and reduced coronary efflux of cardiac troponin I (cTnI) to 2507±359 ng/g heart weight vs. 4693±343 ng/g in CTL (n=12 both groups, p <0.05 each comparison). Treatment with BAY in the first two min of reperfusion mimicked beneficial effects of PostCon in WT hearts (LVDP: 64.7±2.0 % baseline, EDP: 16.2±2.0 mmHg, cTnI: 3311±366; n=13, not significant compared to respective PostCon values). Real-time PCR confirmed absence of A 2B AR in A 2B KO hearts and demonstrated no changes in expression of other adenosine receptor subtypes compared with WT hearts. In A 2B KO hearts, neither PostCon nor BAY improved recovery of LVDP (50.8±1.6 % baseline for CTL vs. 54.5±1.7 % with PostCon vs. 53.0±1.4 with BAY; n=6 each group), and neither affected EDP or release of cTnI. During reperfusion, both PostCon and BAY increased survival kinase signaling through Akt and ERK1/2 phosphorylation in WT but not A 2B KO hearts. In non-ischemic WT hearts, Akt and ERK1/2 phosphorylation was increased by both BAY treatment and application of the PostCon stimulus. These data demonstrate that the protective effects of PostCon are attenuated by targeted deletion of A 2B AR and are mimicked by selective A 2B AR activation, suggesting A 2B AR activation is an important trigger leading to PostCon-induced myocardial protection.

Selectivity of Cyclic [d-Nal7] and [d-Phe7] Substituted MSH Analogues for the Melanocortin Receptor Subtypes

Peptides ◽  
1997 ◽  
Vol 18 (7) ◽  
pp. 1009-1013 ◽  
Author(s):  
Helgi B Schiöth ◽  
Ruta Muceniece ◽  
Felikss Mutulis ◽  
Peteris Prusis ◽  
Gunnar Lindeberg ◽  
...  
Keyword(s):  
Melanocortin Receptor ◽  
Receptor Subtypes

scholarly journals Identification of avian alpha-melanocyte-stimulating hormone in the eye: temporal and spatial regulation of expression in the developing chicken

2001 ◽  
Vol 168 (3) ◽  
pp. 527-537 ◽  
Author(s):  
K Teshigawara ◽  
S Takahashi ◽  
T Boswell ◽  
Q Li ◽  
S Tanaka ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Neural Retina ◽  
Melanocortin Receptor ◽  
Receptor Subtypes ◽  
Peripheral Tissues ◽  
Rpe Cells ◽  
Melanocyte Stimulating Hormone ◽  
Cone Cells ◽  
Stimulating Hormone

The presence and possible physiological roles of alpha-melanocyte-stimulating hormone (alpha-MSH) in the peripheral tissues of birds have not been established. By a combination of RT-PCR, immunocytochemistry and in situ hybridization, we have examined alpha-MSH expression in the eye of the chicken during development. In the 1-day-old chick, alpha-MSH was expressed in the retinal pigment epithelial (RPE) cells, and also at a lower level in the cone cells. The melanocortin receptor subtypes, CMC1, CMC4 and CMC5, were expressed in the layers of the choroid and the neural retina, but not in the RPE cells. It is probable that the RPE cells secrete alpha-MSH to exert paracrine effects on the choroid and neural retina. During embryonic development, alpha-MSH immunoreactivity in the RPE cells was initially detected at embryonic day 10, and increased in intensity as development proceeded. No cone cells were stained with anti-alpha-MSH antiserum in any of the embryonic stages tested. The immunoreactivities for two prohormone convertases, PC1 and PC2, were co-localized to the RPE cells with a pattern of staining similar to that of alpha-MSH. Despite containing alpha-MSH immunoreactivity, the RPE cells in 1-day-old chicks expressed no immunoreactivity for the endoproteases. Furthermore, in a 3-day-old chick, pro-opiomelanocortin mRNA was detectable by in situ hybridization only in the photoreceptor layer and not in the RPE cells. These results suggest that the RPE cells and the cone cells are intraocular sources of alpha-MSH in the embryonic and postnatal life of the chicken respectively. Embryonic expression of alpha-MSH in the RPE cells implies a possible role for the peptide in ocular development.

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