scholarly journals Melanocortin receptors in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Vanni Caruso ◽  
Biao-Xin Chai ◽  
Adrian J. L. Clark ◽  
Roger D. Cone ◽  
Alex N. Eberle ◽  
...  
Keyword(s):  
Clinical Development ◽  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Related Protein ◽  
Erythropoietic Protoporphyria ◽  
The Us ◽  
Function Test ◽  
Us Fda ◽  
Diagnostic Agent ◽  
Agouti Related Protein

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development.

scholarly journals Melanocortin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Vanni Caruso ◽  
Biao-Xin Chai ◽  
Adrian J. L. Clark ◽  
Roger D. Cone ◽  
Alex N. Eberle ◽  
...  
Keyword(s):  
Clinical Development ◽  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Related Protein ◽  
Erythropoietic Protoporphyria ◽  
The Us ◽  
Function Test ◽  
Us Fda ◽  
Diagnostic Agent ◽  
Agouti Related Protein

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [36]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development.

scholarly journals Differential regulation of agouti-related protein and neuropeptide Y in hypothalamic neurons following a stressful event

2005 ◽  
Vol 35 (1) ◽  
pp. 159-164 ◽  
Author(s):  
Martien J H Kas ◽  
Adrie W Bruijnzeel ◽  
Jurgen R Haanstra ◽  
Victor M Wiegant ◽  
Roger A H Adan
Keyword(s):  
Neuropeptide Y ◽  
Hpa Axis ◽  
Arcuate Nucleus ◽  
Eating Behaviour ◽  
Melanocortin Receptor ◽  
Stressful Event ◽  
Mrna Levels ◽  
Related Protein ◽  
Increased Sensitivity ◽  
Agouti Related Protein

Stress affects eating behaviour in rodents and humans, suggesting that the regulation of energy balance and the stress response are coupled physiological processes. Neuropeptide Y (NPY) and agouti-related protein (AgRP) are potent food-stimulating neuropeptides that are highly co-localised in arcuate nucleus neurons of the hypothalamus. Recent studies have shown that NPY and AgRP mRNA levels in these neurons respond similarly to fasting and leptin, indicating functional redundancy of the neuropeptide systems in these orexigenic neurons. However, we have found that NPY and AgRP mRNA expression in arcuate nucleus neurons are dissociated immediately following a stressful event. Two hours following a brief session of inescapable foot shocks, AgRP mRNA levels are down-regulated (P < 0.0001). In contrast, NPY mRNA levels are up-regulated (P < 0.0001). To provide physiological relevance for this acute down-regulation of AgRP, an inverse agonist of melanocortin receptors, we have shown that acute intracerebroventricular injection of a melanocortin receptor agonist, α-melanocyte-stimulating hormone (α-MSH), caused a significantly stronger activation of the hypothalamus–pituitary–adrenal-cortical (HPA) axis following a stressful event than in controls. Thus, AgRP and NPY mRNA levels in similar arcuate nucleus neurons are differentially regulated following a stressful event. This may contribute to increased sensitivity for α-MSH to activate the HPA axis following a repeated stressful experience.

The Clinical Development of the First Recombinant FVIII From a Human Cell Line.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4439-4439
Author(s):  
Sigurd Knaub ◽  
Nadezhda Zozulya
Keyword(s):  
Cell Line ◽  
Human Cell ◽  
Safety Issue ◽  
Data Monitoring Committee ◽  
Human Cell Line ◽  
Clinical Development ◽  
Advisory Committees ◽  
The Us ◽  
Us Fda ◽  
Recombinant Fviii

Abstract Abstract 4439 Objective In order to provide a new recombinant FVIII to the hemophilia community with potentially improved features including improved VWF binding and reduced immunogenic potential, a recombinant FVIII produced in a human cell line was developed (human-cl rhFVIII). The requirements for registration of a new recombinant FVIII in Europe are specified in a guideline. In addition, any global development plans need to be discussed with the US FDA. Methods The clinical development plan of human-cl rhFVIII follows the European guideline and the requirements as discussed with the FDA. Here we introduce the first recently started clinical trial with human-cl rhFVIII. It is a prospective, randomized, open, cross-over phase II pharmacokinetic and efficacy/safety trial in 20 patients with severe hemophilia A conducted at one center in Russia. In this trial the pharmacokinetic properties of human-cl rhFVIII will be compared with an established rFVIII product. After a wash-out phase of at least 72 hours patients will be randomly assigned to one of the two products and receive a single dose of 50 IU of FVIII/kg B.W.. Thereafter, blood will be collected at pre-specified time points over 48 hours, followed by a wash-out phase after which the second product will be administered. Subsequently, patients will be prophylactically treated for 6 months with human-cl rhFVIII to document the efficacy and safety of the product. At the end of the study, a second PK assessment with human-cl rh FVIII will be conducted. FVIII:C will be measured with validated one-stage and chromogenic assays. An “Independent Data Monitoring Committee“ will supervise the safety aspects of the trials and will perform an independent adjudication of the hemostatic efficacy assessment. Results Seven patients have been enrolled and followed for 2 – 50 exposure days on prophylactic treatment. The data of the first 7 patients indicate similar PK characteristics for human-cl rhFVIII compared to the established rFVIII. Human-cl rhFVIII was well tolerated and no safety issue has been reported yet. There were two breakthrough bleeds in target joints in two patients that were controlled with one dose of human-cl rhFVIII each. Further patients have been enrolled and updated information will be presented accordingly. Conclusion The novel human-cl rhFVIII has been successfully introduced to patients and appears to have comparable PK characteristics to a well-established marketed rFVIII and seems to be safe and well tolerated in this limited patient group. A first clinical study with human-cl rhFVIII in the US is planned to be initiated soon. Disclosures: Knaub: Octapharma AG: Employment. Zozulya:Octapharma AG: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Agouti-Related Protein Antagonizes Glucocorticoid Production Induced through Melanocortin 4 Receptor Activation in Bovine Adrenal Cells: A Possible Autocrine Control

Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 541-547 ◽  
Author(s):  
Mabrouka Doghman ◽  
Philippe Delagrange ◽  
Antonine Blondet ◽  
Marie-Claude Berthelon ◽  
Philippe Durand ◽  
...  
Keyword(s):  
Receptor Activation ◽  
Melanocortin Receptor ◽  
Pcr Analysis ◽  
Dependent Manner ◽  
Related Protein ◽  
Peripheral Tissues ◽  
Adrenal Cells ◽  
Autocrine Control ◽  
Glucocorticoid Production ◽  
Agouti Related Protein

Abstract Agouti-related protein (Agrp), primarily expressed in the hypothalamus, is an endogenous antagonist of αMSH at the level of melanocortin 3 receptor (MC3-R) and MC4-R, but the adrenal gland represents the second major Agrp-expressing tissue. In adrenal fasciculata cells, the glucocorticoid secretion is under the control of ACTH, which binds specifically MC2-R, the only functional melanocortin receptor described in these cells to date. Nevertheless, using cultured bovine fasciculata adrenal cells, we report that Agrp has no antagonistic properties against ACTH at the level of MC2-R. In our studies, (Nle4, d-Phe7)-αMSH (NDP-αMSH) stimulated the production of cortisol in a dose-dependent manner, and these effects were abolished by Agrp or SHU9119, a synthetic antagonist of MC3-R and MC4-R. Using a more specific antagonist (JKC-363) and RT-PCR analysis, we can postulate that the effects of NDP-αMSH were mediated via MC4-R. These results are suggestive that adrenal glucocorticoid production could be regulated through MC4-R that may have some relevance in the physiology of adrenal cells. Moreover, Agrp might exert an autocrine control on adrenal cells because a protein with biological Agrp-like activity is secreted by these cells. This peptide could then modulate locally the functions of some peripheral tissues such as adrenals.

High-Resolution NMR Structure of the Chemically-Synthesized Melanocortin Receptor Binding Domain AGRP(87−132) of the Agouti-Related Protein†,‡

Biochemistry ◽  
2001 ◽  
Vol 40 (51) ◽  
pp. 15520-15527 ◽  
Author(s):  
Joseph C. McNulty ◽  
Darren A. Thompson ◽  
Kimberly A. Bolin ◽  
Jill Wilken ◽  
Gregory S. Barsh ◽  
...  
Keyword(s):  
High Resolution ◽  
Receptor Binding ◽  
Binding Domain ◽  
Nmr Structure ◽  
Melanocortin Receptor ◽  
Receptor Binding Domain ◽  
Related Protein ◽  
High Resolution Nmr ◽  
Agouti Related Protein

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.

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