scholarly journals Data for amino acid alignment of Japanese stingray melanocortin receptors with other gnathostome melanocortin receptor sequences, and the ligand selectivity of Japanese stingray melanocortin receptors

Data in Brief ◽  
2016 ◽  
Vol 7 ◽  
pp. 1670-1677 ◽  
Author(s):  
Akiyoshi Takahashi ◽  
Perry Davis ◽  
Christina Reinick ◽  
Kanta Mizusawa ◽  
Tatsuya Sakamoto ◽  
...  
Keyword(s):  
Amino Acid ◽  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Ligand Selectivity ◽  
Amino Acid Alignment

scholarly journals In Silico Finding of Key Interaction Mediated α3β4 and α7 Nicotinic Acetylcholine Receptor Ligand Selectivity of Quinuclidine-Triazole Chemotype

2020 ◽  
Vol 21 (17) ◽  
pp. 6189
Author(s):  
Kuntarat Arunrungvichian ◽  
Sumet Chongruchiroj ◽  
Jiradanai Sarasamkan ◽  
Gerrit Schüürmann ◽  
Peter Brust ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
In Silico ◽  
Amino Acid Residues ◽  
Nicotinic Acetylcholine ◽  
Selective Binding ◽  
Ligand Selectivity ◽  
Α7 Nachr ◽  
Nachr Subtype

The selective binding of six (S)-quinuclidine-triazoles and their (R)-enantiomers to nicotinic acetylcholine receptor (nAChR) subtypes α3β4 and α7, respectively, were analyzed by in silico docking to provide the insight into the molecular basis for the observed stereospecific subtype discrimination. Homology modeling followed by molecular docking and molecular dynamics (MD) simulations revealed that unique amino acid residues in the complementary subunits of the nAChR subtypes are involved in subtype-specific selectivity profiles. In the complementary β4-subunit of the α3β4 nAChR binding pocket, non-conserved AspB173 through a salt bridge was found to be the key determinant for the α3β4 selectivity of the quinuclidine-triazole chemotype, explaining the 47–327-fold affinity of the (S)-enantiomers as compared to their (R)-enantiomer counterparts. Regarding the α7 nAChR subtype, the amino acids promoting a however significantly lower preference for the (R)-enantiomers were the conserved TyrA93, TrpA149 and TrpB55 residues. The non-conserved amino acid residue in the complementary subunit of nAChR subtypes appeared to play a significant role for the nAChR subtype-selective binding, particularly at the heteropentameric subtype, whereas the conserved amino acid residues in both principal and complementary subunits are essential for ligand potency and efficacy.

scholarly journals Hypothalamic and Hindbrain Melanocortin Receptors Contribute to the Feeding, Thermogenic, and Cardiovascular Action of Melanocortins

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5351-5361 ◽  
Author(s):  
Karolina P. Skibicka ◽  
Harvey J. Grill
Keyword(s):  
Energy Expenditure ◽  
Nucleus Tractus Solitarius ◽  
Melanocortin Receptor ◽  
Ventrolateral Medulla ◽  
Melanocortin Receptors ◽  
Projection Neurons ◽  
Response Profile ◽  
Feeding Effects ◽  
Retrochiasmatic Area ◽  
Stimulation Of

Abstract Forebrain ventricular delivery of melanocortin receptor (MC3/4R) agonist increases energy expenditure and decreases food intake (FI). Because forebrain ventricular delivery provides ligand to various anatomically distributed MC3/4R-bearing nuclei, it is unclear which of the receptor subpopulations contributes to the feeding suppression and the sympathetic-thermogenic effects observed. The literature indicates that reexpression of MC4R in the paraventricular nucleus (PVH) affects the feeding but not the energetic phenotype of the MC4R knockout, suggesting that divergent MC4R populations mediate energy expenditure (hindbrain) and FI (hypothalamus) effects of stimulation. Not consistent with this view are data indicating that PVH sympathetic projection neurons express MC4Rs and that feeding effects are induced from hindbrain MC4R sites. Therefore, we hypothesize an opposing perspective: that stimulation of anatomically diverse MC3/4R-bearing nuclei triggers energetic as well as feeding effects. To test this hypothesis, ventricle subthreshold doses of MC3/4R agonist (5 and 10 pmol) were applied in separate experiments to six hindbrain and hypothalamic sites; core temperature (Tc), heart rate (HR), spontaneous activity (SPA), and FI were measured in behaving rats. Nucleus tractus solitarius and PVH stimulation increased Tc, HR, and SPA and decreased FI. Rostral ventrolateral medulla, parabrachial nucleus, and retrochiasmatic area stimulation increased Tc, HR, but not SPA, and decreased FI. The response profile differed to some extent for each nucleus tested, suggesting differential output circuitries for the measured parameters. Data are consistent with the view that energetic and feeding responses are not controlled by regionally divergent MC3/4Rs and can be elicited from multiple, anatomically distributed MC3/4R populations.

Activation of central melanocortin-4 receptor suppresses lipopolysaccharide-induced fever in rats

2003 ◽  
Vol 284 (6) ◽  
pp. R1595-R1603 ◽  
Author(s):  
Partha S. Sinha ◽  
Helgi B. Schiöth ◽  
Jeffrey B. Tatro
Keyword(s):  
Systemic Treatment ◽  
Core Body Temperature ◽  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Antipyretic Effect ◽  
Selective Agonist ◽  
Melanocortin 4 Receptor ◽  
Heat Conservation ◽  
Core Body ◽  
Escherichia Coli Lipopolysaccharide

Activation of central melanocortin receptors (MCR) inhibits fever, but the identity of the MCR subtype(s) mediating this antipyretic effect is unknown. To determine whether selective central melanocortin receptor-4 (MC4R) activation produces antipyretic effects, the MC4R selective agonist MRLOB-0001 (CO-His-d-Phe-Arg-Trp-Dab-NH2) was administered intracerebroventricularly to rats treated with Escherichia coli lipopolysaccharide (LPS, 30 μg/kg ip). Treatment with MRLOB-0001 (150 ng icv) did not lower core body temperature (Tc) in afebrile rats but did suppress LPS-induced increases in Tc and associated decreases in tail skin temperature (Tsk), an indicator of vasomotor thermoeffector function. In contrast, systemic treatment with MRLOB-0001 (150 ng iv) did not produce similar antipyretic effects. Coadministration of the selective MC4R antagonist HS014 (1 μg icv) blocked the antipyretic effects of MRLOB-0001. HS014 alone (1 μg icv) had no significant effect on LPS-induced increases in Tc or decreases in Tsk and in afebrile rats had no significant effects on Tc or Tsk. We conclude that pharmacological activation of central MC4R suppresses febrile increases in Tc and that inhibition of heat conservation pathways may contribute to this effect. These findings suggest that the central MC4R may mediate the long-recognized antipyretic effects of centrally administered melanocortins.

scholarly journals NucAmino: a nucleotide to amino acid alignment optimized for virus gene sequences

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Philip L. Tzou ◽  
Xiaoqiu Huang ◽  
Robert W. Shafer
Keyword(s):  
Amino Acid ◽  
Gene Sequences ◽  
Virus Gene ◽  
Amino Acid Alignment

Involvement of melanocortin receptor accessory proteins (MRAPs) in the function of melanocortin receptors

2013 ◽  
Vol 188 ◽  
pp. 133-136 ◽  
Author(s):  
J.M. Cerdá-Reverter ◽  
M.J. Agulleiro ◽  
R. Cortés ◽  
E. Sánchez ◽  
R. Guillot ◽  
...  
Keyword(s):  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Accessory Proteins

scholarly journals Melanocortin receptor-mediated mobilization of intracellular free calcium in HEK293 cells

2001 ◽  
Vol 5 (1) ◽  
pp. 11-19 ◽  
Author(s):  
KATHLEEN G. MOUNTJOY ◽  
PHILIP L. KONG ◽  
JOHN A. TAYLOR ◽  
DERRIL H. WILLARD ◽  
WILLIAM O. WILKISON
Keyword(s):  
Intracellular Free Calcium ◽  
Melanocortin Receptor ◽  
Hek293 Cells ◽  
Melanocortin Receptors ◽  
Calcium Signal ◽  
Free Calcium ◽  
Agouti Protein ◽  
Transient Rise ◽  
Physiological Relevance ◽  
Free Calcium Concentration

Mouse melanocortin receptors, MC1-R, MC3-R, MC4-R, and MC5-R, when expressed in HEK293 cells and stimulated with either α-melanocyte-stimulating hormone (α-MSH) or desacetyl-α-MSH, mediate increases in intracellular free calcium concentration ([Ca2+]i) with EC50 values between 0.3 and 4.3 nM. The increase in [Ca2+]i is cholera toxin sensitive and pertussis toxin insensitive. The mechanism involves calcium mobilization from intracellular stores without a transient rise in inositol trisphosphate. Mouse agouti protein (55 nM) is a competitive antagonist of α-MSH (6-fold) and desacetyl-α-MSH (8-fold), coupling the mMC1-R to increased [Ca2+]i. Agouti protein (55 nM) significantly increased the EC50 for α-MSH (3-fold), and 550 nM agouti protein significantly increased the EC50 for desacetyl-α-MSH (4-fold), coupling the mMC4-R to a rise in [Ca2+]i. However, agouti protein antagonism of the MC4-R may not be competitive since there was a trend for the maximum response to also increase. There was no significant antagonism of the MC3-R and MC5-R by agouti protein (55 nM). Understanding the physiological relevance of the transduction of a calcium signal by melanocortin peptides may be important for future development of therapeutic targeting of the melanocortin receptors.

scholarly journals ERG11 Polymorphism in Voriconazole-Resistant Candida tropicalis: Weak Role of ERG11 Expression, Ergosterol Content, and Membrane Permeability

2020 ◽  
Vol 65 (1) ◽  
pp. e00325-20
Author(s):  
Patricia Navarro-Rodríguez ◽  
Loida López-Fernández ◽  
Adela Martin-Vicente ◽  
Josep Guarro ◽  
Javier Capilla
Keyword(s):  
Amino Acid ◽  
Membrane Permeability ◽  
Candida Tropicalis ◽  
Gene Sequencing ◽  
Missense Mutations ◽  
Sterol Content ◽  
Content Type ◽  
Ergosterol Content ◽  
Amino Acid Alignment

ABSTRACTMutations in ERG11 were detected by gene sequencing and amino acid alignment in 18 Candida tropicalis strains with different degrees of sensitivity to voriconazole (VRC). ERG11 expression, sterol content, and membrane permeability were also evaluated. We report three missense mutations in ERG11 that resulted in resistance to VRC. The transcriptional levels of ERG11 as well as the ergosterol content and membrane permeability demonstrated no correlation to only a slight correlation with the obtained MIC values, but the data did suggest a tendency toward such a correlation.

scholarly journals MOLECULAR EVOLUTION OF GPCRS: Melanocortin/melanocortin receptors

2014 ◽  
Vol 52 (3) ◽  
pp. T29-T42 ◽  
Author(s):  
Robert M Dores ◽  
Richard L Londraville ◽  
Jeremy Prokop ◽  
Perry Davis ◽  
Nathan Dewey ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Focal Point ◽  
Cartilaginous Fish ◽  
G Protein Coupled Receptors ◽  
Melanocortin Receptors ◽  
Accessory Proteins ◽  
Melanocortin 1 Receptor ◽  
Ligand Selectivity ◽  
G Protein Coupled ◽  
Receptor Accessory Protein

The melanocortin receptors (MCRs) are a family of G protein-coupled receptors that are activated by melanocortin ligands derived from the proprotein, proopiomelanocortin (POMC). During the radiation of the gnathostomes, the five receptors have become functionally segregated (i.e. melanocortin 1 receptor (MC1R), pigmentation regulation; MC2R, glucocorticoid synthesis; MC3R and MC4R, energy homeostasis; and MC5R, exocrine gland physiology). A focus of this review is the role that ligand selectivity plays in the hypothalamus/pituitary/adrenal–interrenal (HPA–I) axis of teleosts and tetrapods as a result of the exclusive ligand selectivity of MC2R for the ligand ACTH. A second focal point of this review is the roles that the accessory proteins melanocortin 2 receptor accessory protein 1 (MRAP1) and MRAP2 are playing in, respectively, the HPA–I axis (MC2R) and the regulation of energy homeostasis by neurons in the hypothalamus (MC4R) of teleosts and tetrapods. In addition, observations are presented on trends in the ligand selectivity parameters of cartilaginous fish, teleost, and tetrapod MC1R, MC3R, MC4R, and MC5R paralogs, and the modeling of the HFRW motif of ACTH(1–24) when compared with α-MSH. The radiation of the MCRs during the evolution of the gnathostomes provides examples of how the physiology of endocrine and neuronal circuits can be shaped by ligand selectivity, the intersession of reverse agonists (agouti-related peptides (AGRPs)), and interactions with accessory proteins (MRAPs).

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.

60 YEARS OF POMC: Melanocortin receptors: evolution of ligand selectivity for melanocortin peptides

2016 ◽  
Vol 56 (4) ◽  
pp. T119-T133 ◽  
Author(s):  
Robert M Dores ◽  
Liang Liang ◽  
Perry Davis ◽  
Alexa L Thomas ◽  
Bogdana Petko
Keyword(s):  
Amino Acid Sequences ◽  
Melanocortin Receptors ◽  
Accessory Protein ◽  
Ligand Selectivity ◽  
Common Precursor ◽  
Melanocortin Peptides ◽  
Genome Duplications ◽  
Duplication Events ◽  
High Conservation ◽  
Early Radiation

The evolution of the melanocortin receptors (MCRs) is linked to the evolution of adrenocorticotrophic hormone (ACTH), the melanocyte-stimulating hormones (MSHs), and their common precursor pro-opiomelanocortin (POMC). The origin of the MCRs and POMC appears to be grounded in the early radiation of the ancestral protochordates. During the genome duplications that have occurred during the evolution of the chordates, the organization plan for POMC was established, and features that have been retained include, the high conservation of the amino acid sequences of α-MSH and ACTH, and the presence of the HFRW MCR activation motif in all of the melanocortin peptides (i.e. ACTH, α-MSH, β-MSH, γ-MSH, and δ-MSH). For the MCRs, the chordate genome duplication events resulted in the proliferation of paralogous receptor genes, and a divergence in ligand selectivity. While most gnathostome MCRs can be activated by either ACTH or the MSHs, teleost and tetrapod MC2R orthologs can only be activated by ACTH. The appearance of the accessory protein, MRAP1, paralleled the emergence of teleost and tetrapods MC2R ligand selectivity, and the dependence of these orthologs on MRAP1 for trafficking to the plasma membrane. The accessory protein, MRAP2, does not affect MC2R ligand selectivity, but does influence the functionality of MC4R orthologs. In this regard, the roles that these accessory proteins may play in the physiology of the five MCRs (i.e. MC1R, MC2R, MC3R, MC4R, and MC5R) are discussed.

Sign in / Sign up

Export Citation Format

Share Document