scholarly journals Melanocortin Receptor 4 (MC4R) Signaling System in Nile Tilapia

2020 ◽  
Vol 21 (19) ◽  
pp. 7036
Author(s):  
Tianqiang Liu ◽  
Yue Deng ◽  
Zheng Zhang ◽  
Baolong Cao ◽  
Jing Li ◽  
...  
Keyword(s):  
Amino Acid Identity ◽  
Melanocortin Receptor ◽  
Signaling System ◽  
Melanocyte Stimulating Hormone ◽  
High Amino Acid ◽  
Agonist And Antagonist ◽  
Agouti Related Protein ◽  
High Amino Acid Identity ◽  
Receptor Accessory Protein

The melanocortin receptor 4 (MC4R) signaling system consists of MC4R, MC4R ligands [melanocyte-stimulating hormone (MSH), adrenocorticotropin (ACTH), agouti-related protein (AgRP)], and melanocortin-2 receptor accessory protein 2 (MRAP2), and it has been proposed to play important roles in feeding and growth in vertebrates. However, the expression and functionality of this system have not been fully characterized in teleosts. Here, we cloned tilapia MC4R, MRAP2b, AgRPs (AgRP, AgRP2), and POMCs (POMCa1, POMCb) genes and characterized the interaction of tilapia MC4R with MRAP2b, AgRP, α-MSH, and ACTH in vitro. The results indicate the following. (1) Tilapia MC4R, MRAP2b, AgRPs, and POMCs share high amino acid identity with their mammalian counterparts. (2) Tilapia MRAP2b could interact with MC4R expressed in CHO cells, as demonstrated by Co-IP assay, and thus decrease MC4R constitutive activity and enhance its sensitivity to ACTH1-40. (3) As in mammals, AgRP can function as an inverse agonist and antagonist of MC4R, either in the presence or absence of MRAP2b. These data, together with the co-expression of MC4R, MRAP2b, AgRPs, and POMCs in tilapia hypothalamus, suggest that as in mammals, ACTH/α-MSH, AgRP, and MRAP2 can interact with MC4R to control energy balance and thus play conserved roles in the feeding and growth of teleosts.

scholarly journals Complete Genome Sequence of Murine Pneumotropic Virus (Polyomaviridae) Clone pKV(37-1)

2016 ◽  
Vol 4 (3) ◽  
Author(s):  
Jane E. Libbey ◽  
Robert S. Fujinami
Keyword(s):  
Regulatory Region ◽  
Viral Proteins ◽  
Amino Acid Identity ◽  
Virus Genome ◽  
T Antigens ◽  
Protein Coding ◽  
Coding Regions ◽  
High Amino Acid ◽  
Multiple Regions ◽  
High Amino Acid Identity

The murine pneumotropic virus genome encoded by the pKV(37-1) clone was sequenced to completion. The regulatory region harbored a mutation not previously reported. The protein coding regions (large and small T antigens, viral proteins 1 to 3) showed multiple regions of high amino acid identity to the human, simian, and bovine polyomaviruses.

Prevention of reflex natriuresis after acute unilateral nephrectomy by melanocortin receptor antagonists

1998 ◽  
Vol 274 (4) ◽  
pp. R931-R938 ◽  
Author(s):  
Xi-Ping Ni ◽  
Robert A. Kesterson ◽  
Shubh D. Sharma ◽  
Victor J. Hruby ◽  
Roger D. Cone ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Urinary Sodium Excretion ◽  
Melanocortin Receptor ◽  
Unilateral Nephrectomy ◽  
Sprague Dawley ◽  
Receptor Antagonists ◽  
Pharmacological Characterization ◽  
Melanocyte Stimulating Hormone ◽  
Sprague Dawley Rats

γ-Melanocyte-stimulating hormone (γ-MSH), atrial natriuretic peptide (ANP), and oxytocin have been identified as candidate hormonal mediators of the reflex natriuresis that follows acute unilateral nephrectomy (AUN). Pharmacological characterization of the third melanocortin receptor (MC3-R) indicates that it uniquely responds to physiological concentrations of γ-MSH. We tested the roles of γ-MSH, ANP, and oxytocin in the postnephrectomy natriuresis by carrying out AUN during continuous intrarenal infusion of specific antagonists for their cognate receptors. In anesthetized Sprague-Dawley rats, urinary sodium excretion (UNaV) increased from 0.34 ± 0.04 to 1.12 ± 0.11 μeq/min 90 min after AUN ( P < 0.001). No change in UNaV occurred in rats undergoing a sham AUN procedure. Plasma immunoreactive γ-MSH concentration was 53 ± 8 fmol/ml after sham AUN but 112 ± 17 fmol/ml after AUN ( P < 0.01). SHU-9119 and SHU-9005 are substituted derivatives of α-MSH with potent antagonism at the MC3-R in vitro. Infusion of these compounds at 5 pmol/min completely blocked the natriuretic response to AUN despite a similar elevation in plasma γ-MSH (111 ± 12 vs. 49 ± 8 fmol/ml in sham rats, P < 0.01). Intrarenal infusion of the ANP receptor antagonist A-71915 (5 pmol/min) or the oxytocin receptor antagonist [d(CH2)5 1, Tyr(Me)2,Orn8] vasotocin (10 pmol/min) effectively inhibited the natriuresis induced by intravenous infusion of ANP or oxytocin (each at 1 pmol/min), respectively, but did not block the natriuresis after AUN. Plasma immunoreactivity of these peptides was not increased after AUN. These results indicate that reflex natriuresis after AUN is accompanied by an increase in plasma γ-MSH but not ANP or oxytocin concentration and is prevented by intrarenal infusion of receptor antagonists with selectivity for MC3-R. The data indicate that γ-MSH or a closely related peptide mediates postnephrectomy natriuresis and provide further support for the possibility that γ-MSH may play a wider role in sodium homeostasis.

scholarly journals Paraventricular Nucleus Administration of Calcitonin Gene-Related Peptide Inhibits Food Intake and Stimulates the Hypothalamo-Pituitary-Adrenal Axis

Endocrinology ◽  
2003 ◽  
Vol 144 (4) ◽  
pp. 1420-1425 ◽  
Author(s):  
Waljit S. Dhillo ◽  
Caroline J. Small ◽  
Preeti H. Jethwa ◽  
Sabina H. Russell ◽  
James V. Gardiner ◽  
...  
Keyword(s):  
Food Intake ◽  
Hpa Axis ◽  
Male Rats ◽  
Mrna Levels ◽  
Related Protein ◽  
Melanocyte Stimulating Hormone ◽  
Calcitonin Gene ◽  
Agouti Related Protein ◽  
Prior Administration

Abstract Calcitonin gene-related protein (CGRP) inhibits food intake and stimulates the hypothalamo-pituitary-adrenal (HPA) axis after intracerebroventricular injection in rats. However, the hypothalamic site and mechanism of action are unknown. We investigated the effects of intraparaventricular nucleus administration (iPVN) of CGRP on food intake and the HPA axis in rats and the effect of CGRP on the release of hypothalamic neuropeptides in vitro. In addition, we investigated the effects of food deprivation on hypothalamic CGRP expression. CGRP dose-dependently reduced food intake in the first hour after iPVN injection in fasted male rats (saline, 5.1 ± 0.8 g; 0.3 nmol CGRP, 1.1 ± 0.5 g; P &lt; 0.001 vs. saline). iPVN injection of CGRP8–37 (a CGRP1 receptor antagonist) alone had no effect on food intake. However, the reduction in food intake by iPVN CGRP was attenuated by prior administration of CGRP8–37 [CGRP8–37 (10 nmol)/CGRP (0.3 nmol), 3.0 ± 0.8 g; P &lt; 0.05 vs. 0.3 nmol CGRP]. CGRP (100 nm) stimulated the release of α-melanocyte stimulating hormone, cocaine- and amphetamine-related transcript, corticotropin-releasing hormone, and arginine vasopressin from hypothalamic explants to 127 ± 19%, 148 ± 10%, 158 ± 17%, and 198 ± 21% of basal levels, respectively (P &lt; 0.05 vs. basal), but did not alter the release of either neuropeptide Y or agouti-related protein. Hypothalamic CGRP mRNA levels in 24-h fasted rats were increased to 130 ± 8% of control levels [CGRP mRNA (arbitrary units), 4.75 ± 0.4; controls, 3.65 ± 0.34; P &lt; 0.05]. Our data suggest that CGRP administered to the PVN inhibits food intake and stimulates the HPA axis.

scholarly journals Activation of melanocortin receptors in the intermediolateral cell column of the upper thoracic cord elicits tachycardia in the rat

2013 ◽  
Vol 305 (6) ◽  
pp. H885-H893 ◽  
Author(s):  
Masamitsu Iwasa ◽  
Kazumi Kawabe ◽  
Hreday N. Sapru
Keyword(s):  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Cell Column ◽  
Melanocyte Stimulating Hormone ◽  
Hypothalamic Arcuate Nucleus ◽  
Male Wistar Rats ◽  
Thoracic Cord ◽  
The Right ◽  
Upper Thoracic ◽  
Agouti Related Protein

Melanocortin receptors (MCRs) are present in the intermediolateral cell column of the spinal cord (IML). We tested the hypothesis that activation of MCRs in the IML elicits cardioacceleratory responses and the source of melanocortins in the IML may be the melanocortin-containing neurons in the hypothalamic arcuate nucleus (ARCN). Experiments were done in urethane-anesthetized, artificially ventilated adult male Wistar rats. Microinjections (50 nl) of α-melanocyte stimulating hormone (α-MSH) (0.4–2 mM) and adrenocorticotropic hormone (ACTH) (0.5–2 mM) into the right IML elicited increases in heart rate (HR). These tachycardic responses were blocked by microinjections of melanocortin receptor 4 (MC4R) antagonists [SHU9119 (0.25 mM) or agouti-related protein (AGRP, 0.1 mM)] into the right IML. Stimulation of right ARCN by microinjections (30 nl) of N-methyl-d-aspartic acid (NMDA, 10 mM) elicited increases in HR. Blockade of MC4Rs in the ipsilateral IML at T1–T3 using SHU9119 (0.25 mM) attenuated the tachycardic responses elicited by subsequent microinjections of NMDA into the ipsilateral ARCN. ARCN neurons retrogradely labeled by microinjections of Fluoro-Gold into the right IML showed immunoreactivity for proopiomelanocortin (POMC), α-MSH, and ACTH. Fibers immunoreactive for POMC, α-MSH, and ACTH were present in the IML at T1-T3. These results indicated that activation of MC4Rs in the right IML elicited tachycardia and one of the sources of melanocortins in the IML is the ARCN. Melanocortin levels are elevated in stress and ARCN neurons are activated during stress. Our results allude to the possibility that cardiac effects of stress may be mediated via melanocortin containing ARCN neurons that project to the IML.

scholarly journals Regulation of adipose tissue leptin secretion by alpha-melanocyte-stimulating hormone and agouti-related protein: further evidence of an interaction between leptin and the melanocortin signalling system

2004 ◽  
Vol 32 (1) ◽  
pp. 145-153 ◽  
Author(s):  
N Hoggard ◽  
L Hunter ◽  
JS Duncan ◽  
DV Rayner
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Receptor Subtype ◽  
Related Protein ◽  
Melanocortin System ◽  
Rat Adipocytes ◽  
Melanocyte Stimulating Hormone ◽  
Agouti Related Protein ◽  
Stimulating Hormone

The central role of the melanocortin system in the regulation of energy balance has been studied in great detail. However, the functions of circulating melanocortins and the roles of their peripheral receptors remain to be elucidated. There is increasing evidence of a peripheral action of melanocortins in the regulation of leptin production by adipocytes. Here we investigate the interaction of alpha-melanocyte stimulating hormone (alpha-MSH) and agouti-related protein (AgRP) in the regulation of leptin secretion from cultured rat adipocytes and examine the changes in circulating alpha-MSH and AgRP in lean and obese rodents after hormonal and energetic challenge. Leptin secretion (measured by ELISA) and gene expression (by real-time quantitative PCR) of differentiated rat adipocytes cultured in vitro were inhibited by the administration of alpha-MSH (EC50=0.24 nM), and this effect was antagonised by antagonists of the melanocortin receptors MC4R and MC3R (AgRP and SHU9119). The presence of MC4R in rat adipocytes (RT-PCR and restriction digest) supports the involvement of this receptor subtype in this interaction. Leptin administered to ob/ob mice in turn increases the release of alpha-MSH into the circulation, suggesting a possible feedback loop between the site of alpha-MSH release and the release of leptin from the adipose tissue. However, the physiological significance of this putative feedback probably depends upon the underlying state of energy balance, since in the fasting state low plasma alpha-MSH is paralleled by low plasma leptin.

scholarly journals WNT5B in Physiology and Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Sarocha Suthon ◽  
Rachel S. Perkins ◽  
Vitezslav Bryja ◽  
Gustavo A. Miranda-Carboni ◽  
Susan A. Krum
Keyword(s):  
Diabetes Mellitus ◽  
Cardiac Tissue ◽  
Expression Patterns ◽  
Cell Types ◽  
Amino Acid Identity ◽  
Acid Identity ◽  
High Amino Acid ◽  
Canonical Wnt ◽  
High Amino Acid Identity

WNT5B, a member of the WNT family of proteins that is closely related to WNT5A, is required for cell migration, cell proliferation, or cell differentiation in many cell types. WNT5B signals through the non-canonical β-catenin-independent signaling pathway and often functions as an antagonist of canonical WNT signaling. Although WNT5B has a high amino acid identity with WNT5A and is often assumed to have similar activities, WNT5B often exhibits unique expression patterns and functions. Here, we describe the distinct effects and mechanisms of WNT5B on development, bone, adipose tissue, cardiac tissue, the nervous system, the mammary gland, the lung and hematopoietic cells, compared to WNT5A. We also highlight aberrances in non-canonical WNT5B signaling contributing to diseases such as osteoarthritis, osteoporosis, obesity, type 2 diabetes mellitus, neuropathology, and chronic diseases associated with aging, as well as various cancers.

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