Astressin-B

Last updated
Astressin-B
Astressin-B 2RMB.png
Space-filling model of astressin-B. PDB: 2rmb ​.
Identifiers
  • Cyclo(30-33)(phenylalanyl(12)-norleucyl(21)-Cα-methylleucyl(2-7)-glutamyl(30)-lysyl(33)-norleucyl(38)-Cα-methyleucyl(40))acetyl-hCRF(9-41)
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
Formula C183H305N47O55
Molar mass 4043.727 g·mol−1
3D model (JSmol)
  • CCCC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@](C)(CC(C)C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)NC3CCC(=O)NCCCC[C@H](NC(=O)[C@H](CC(=O)N)NC(=O)[C@@H](CC(=O)N)NC3=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@](C)(CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N
  • InChI=1S/C183H305N47O55/c1-26-30-47-106(201-151(256)107(48-34-39-70-184)202-155(260)112(53-44-75-196-181(192)193)207-169(274)125(80-96(13)14)225-179(284)182(24,87-97(15)16)229-175(280)127(82-105-89-194-91-197-105)220-170(275)126(81-104-45-32-31-33-46-104)219-174(279)132(90-231)224-168(273)124(79-95(11)12)218-173(278)130(85-143(249)250)199-103(23)232)163(268)226-146(100(20)28-3)178(283)214-120(61-69-142(247)248)164(269)227-147(101(21)29-4)177(282)213-119(60-68-141(245)246)161(266)205-108(49-35-40-71-185)152(257)208-113(54-62-133(188)233)157(262)212-117(58-66-139(241)242)159(264)204-109(50-36-41-72-186)153(258)210-116(57-65-138(239)240)158(263)203-110(51-37-42-73-187)154(259)211-118(59-67-140(243)244)160(265)209-115(56-64-137(237)238)150(255)198-102(22)149(254)200-114-55-63-136(236)195-74-43-38-52-111(206-171(276)128(83-134(189)234)222-172(277)129(84-135(190)235)221-162(114)267)156(261)215-121(76-92(5)6)165(270)216-122(77-93(7)8)166(271)217-123(78-94(9)10)167(272)223-131(86-144(251)252)176(281)230-183(25,88-98(17)18)180(285)228-145(148(191)253)99(19)27-2/h31-33,45-46,89,91-102,106-132,145-147,231H,26-30,34-44,47-88,90,184-187H2,1-25H3,(H2,188,233)(H2,189,234)(H2,190,235)(H2,191,253)(H,194,197)(H,195,236)(H,198,255)(H,199,232)(H,200,254)(H,201,256)(H,202,260)(H,203,263)(H,204,264)(H,205,266)(H,206,276)(H,207,274)(H,208,257)(H,209,265)(H,210,258)(H,211,259)(H,212,262)(H,213,282)(H,214,283)(H,215,261)(H,216,270)(H,217,271)(H,218,278)(H,219,279)(H,220,275)(H,221,267)(H,222,277)(H,223,272)(H,224,273)(H,225,284)(H,226,268)(H,227,269)(H,228,285)(H,229,280)(H,230,281)(H,237,238)(H,239,240)(H,241,242)(H,243,244)(H,245,246)(H,247,248)(H,249,250)(H,251,252)(H4,192,193,196)/t99-,100-,101-,102-,106-,107-,108-,109-,110-,111-,112-,113-,114?,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126+,127-,128-,129+,130-,131-,132-,145-,146-,147-,182+,183+/m0/s1
  • Key:BGFHNAZIBICPLD-IXILWOCFSA-N

Astressin-B is a nonselective corticotropin releasing hormone antagonist that reduces the synthesis of adrenocorticotropic hormone and cortisol. [1]

It reduces the synthesis of adrenocorticotropic hormone and improves the sexual drive of rats under stressing conditions. [2]

Astressin-B is able to delay the emptying of solid food in mice. [3] Astressin-B can prevent the release of adrenocorticotropic hormone in mice due to shock, alcohol and endotoxemia. [4]

Treatment with astressin-B caused the sudden growth of hair in mice bred for a propensity for stress. [5]

Related Research Articles

<span class="mw-page-title-main">Adrenocorticotropic hormone</span> Pituitary hormone

Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol and androgens by the zona fasiculata and zona reticularis, respectively. ACTH is also related to the circadian rhythm in many organisms.

<span class="mw-page-title-main">Corticotropin-releasing hormone</span> Mammalian protein found in humans

Corticotropin-releasing hormone (CRH) is a peptide hormone involved in stress responses. It is a releasing hormone that belongs to corticotropin-releasing factor family. In humans, it is encoded by the CRH gene. Its main function is the stimulation of the pituitary synthesis of adrenocorticotropic hormone (ACTH), as part of the hypothalamic–pituitary–adrenal axis.

Corticotropin-releasing factor family, CRF family is a family of related neuropeptides in vertebrates. This family includes corticotropin-releasing hormone, urotensin-I, urocortin, and sauvagine. The family can be grouped into 2 separate paralogous lineages, with urotensin-I, urocortin and sauvagine in one group and CRH forming the other group. Urocortin and sauvagine appear to represent orthologues of fish urotensin-I in mammals and amphibians, respectively. The peptides have a variety of physiological effects on stress and anxiety, vasoregulation, thermoregulation, growth and metabolism, metamorphosis and reproduction in various species, and are all released as prohormones.

Corticotropes are basophilic cells in the anterior pituitary that produce pro-opiomelanocortin (POMC) which undergoes cleavage to adrenocorticotropin (ACTH), β-lipotropin (β-LPH), and melanocyte-stimulating hormone (MSH). These cells are stimulated by corticotropin releasing hormone (CRH) and make up 15–20% of the cells in the anterior pituitary. The release of ACTH from the corticotropic cells is controlled by CRH, which is formed in the cell bodies of parvocellular neurosecretory cells within the paraventricular nucleus of the hypothalamus and passes to the corticotropes in the anterior pituitary via the hypophyseal portal system. Adrenocorticotropin hormone stimulates the adrenal cortex to release glucocorticoids and plays an important role in the stress response.

<span class="mw-page-title-main">Neuropeptide Y</span> Mammalian protein found in Homo sapiens

Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. It is secreted alongside other neurotransmitters such as GABA and glutamate. 

<span class="mw-page-title-main">Vasopressin receptor 1B</span> Protein-coding gene in the species Homo sapiens

Vasopressin V1b receptor (V1BR) also known as vasopressin 3 receptor (VPR3) or antidiuretic hormone receptor 1B is a protein that in humans is encoded by the AVPR1B gene.

<span class="mw-page-title-main">Urocortin</span>

Urocortin is a protein that in humans is encoded by the UCN gene. Urocortin belongs to the corticotropin-releasing factor (CRF) family of proteins which includes CRF, urotensin I, sauvagine, urocortin II and urocortin III. Urocortin is involved in the mammalian stress response, and regulates aspects of appetite and stress response.

Urocortin III, a 38–41 amino acid peptide, is a member of the CRF, also known as CRH family of peptides, with a long evolutionary lineage.

<span class="mw-page-title-main">ACTH receptor</span> Mammalian protein found in Homo sapiens

The adrenocorticotropic hormone receptor or ACTH receptor also known as the melanocortin receptor 2 or MC2 receptor is a type of melanocortin receptor (type 2) which is specific for ACTH. A G protein–coupled receptor located on the external cell plasma membrane, it is coupled to Gαs and upregulates levels of cAMP by activating adenylyl cyclase. The ACTH receptor plays a role in immune function and glucose metabolism.

<span class="mw-page-title-main">Corticotropin-releasing hormone receptor 1</span> Protein and coding gene in humans

Corticotropin-releasing hormone receptor 1 (CRHR1) is a protein, also known as CRF1, with the latter (CRF1) now being the IUPHAR-recommended name. In humans, CRF1 is encoded by the CRHR1 gene at region 17q21.31, beside micrototubule-associated protein tau MAPT.

<span class="mw-page-title-main">Corticotropin-releasing hormone receptor 2</span> Protein found in humans

Corticotropin-releasing hormone receptor 2 (CRHR2) is a protein, also known by the IUPHAR-recommended name CRF2, that is encoded by the CRHR2 gene and occurs on the surfaces of some mammalian cells. CRF2 receptors are type 2 G protein-coupled receptors for corticotropin-releasing hormone (CRH) that are resident in the plasma membranes of hormone-sensitive cells. CRH, a peptide of 41 amino acids synthesized in the hypothalamus, is the principal neuroregulator of the hypothalamic-pituitary-adrenal axis, signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors such as adenylate cyclase. The CRF2 receptor is a multi-pass membrane protein with a transmembrane domain composed of seven helices arranged in a V-shape. CRF2 receptors are activated by two structurally similar peptides, urocortin II, and urocortin III, as well as CRH.

<span class="mw-page-title-main">UCN2</span> Protein-coding gene in the species Homo sapiens

Urocortin-2 is a protein that in humans is encoded by the UCN2 gene.

<span class="mw-page-title-main">UCN3</span> Protein-coding gene in the species Homo sapiens

Urocortin-3 is a protein that, in humans, is encoded by the UCN3 gene. It belongs to the corticotropin-releasing hormone family.

<span class="mw-page-title-main">Antalarmin</span> Chemical compound

Antalarmin (CP-156,181) is a drug that acts as a CRH1 antagonist.

<span class="mw-page-title-main">Pexacerfont</span> Chemical compound

Pexacerfont (INN, previously known as BMS-562,086) is a drug developed by Bristol-Myers Squibb which acts as a CRF1 antagonist.

A Corticotropin-releasing hormone antagonist is a specific type of receptor antagonist that blocks the receptor sites for corticotropin-releasing hormone, also known as corticotropin-releasing factor (CRF), which synchronizes the behavioral, endocrine, autonomic, and immune responses to stress by controlling the hypothalamic-pituitary-adrenal axis. CRH antagonists thereby block the consequent secretions of ACTH and cortisol due to stress, among other effects.

<span class="mw-page-title-main">BIBP-3226</span> Chemical compound

BIBP-3226 is a drug used in scientific research which acts as a potent and selective antagonist for both the Neuropeptide Y receptor Y1 and also the neuropeptide FF receptor. It was the first non-peptide antagonist developed for the Y1 receptor and has been widely used to help determine its functions in the body. Activation of Y1 is thought to be involved in functions such as regulation of appetite and anxiety, and BIBP-3226 has anxiogenic and anorectic effects, as well as blocking the Y1-mediated corticotropin releasing hormone release. It has also been used as a lead compound to develop a number of newer more potent Y1 antagonists.

<span class="mw-page-title-main">Verucerfont</span> Chemical compound

Verucerfont (GSK-561,679) is a drug developed by GlaxoSmithKline which acts as a CRF-1 antagonist. Corticotropin releasing factor (CRF), also known as Corticotropin releasing hormone, is an endogenous peptide hormone which is released in response to various triggers such as chronic stress, and activates the two corticotropin-releasing hormone receptors CRH-1 and CRH-2. This then triggers the release of corticotropin (ACTH), another hormone which is involved in the physiological response to stress.

Sauvagine is a neuropeptide from the corticotropin-releasing factor (CRF) family of peptides and is orthologous to the mammalian hormone, urocortin 1, and the teleost fish hormone, urotensin 1. It is 40 amino acids in length, and has the sequence XGPPISIDLSLELLRKMIEIEKQEKEKQQAANNRLLLDTI-NH2, with a pyrrolidone carboxylic acid modification at the N-terminal and amidation of the C-terminal isoleucine residue. It was originally isolated from the skin of the frog Phyllomedusa sauvagii. Given its relation to other CRF-related peptides, it exerts similar physiological effects as corticotropin-releasing hormone.

<span class="mw-page-title-main">Emicerfont</span> Chemical compound

Emicerfont (GW-876,008) is a drug developed by GlaxoSmithKline which acts as a CRF-1 antagonist. Corticotropin releasing factor (CRF), also known as Corticotropin releasing hormone, is an endogenous peptide hormone which is released in response to various triggers such as chronic stress, and activates the two corticotropin-releasing hormone receptors: CRF1 and CRF2. This then triggers the release of corticotropin (ACTH), another hormone which is involved in the physiological response to stress.

References

  1. ↑ Vulliémoz NR, Xiao E, Xia-Zhang L, Rivier J, Ferin M (March 2008). "Astressin B, a nonselective corticotropin-releasing hormone receptor antagonist, prevents the inhibitory effect of ghrelin on luteinizing hormone pulse frequency in the ovariectomized rhesus monkey". Endocrinology. 149 (3): 869–874. doi:10.1210/en.2007-1350. PMC   2275354 . PMID   18063681.
  2. ↑ Miwa Y, Nagase K, Oyama N, Akino H, Yokoyama O (March 2011). "Effect of corticotropin-releasing factor receptor antagonist on psychologically suppressed masculine sexual behavior in rats". The Journal of Sexual Medicine. 8 (3): 688–695. doi:10.1111/j.1743-6109.2010.02055.x. PMID   20946165.
  3. ↑ Wang L, Martínez V, Rivier JE, Taché Y (November 2001). "Peripheral urocortin inhibits gastric emptying and food intake in mice: differential role of CRF receptor 2". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 281 (5): R1401–R1410. doi: 10.1152/ajpregu.2001.281.5.R1401 . PMID   11641109.
  4. ↑ Rivier CL, Grigoriadis DE, Rivier JE (June 2003). "Role of corticotropin-releasing factor receptors type 1 and 2 in modulating the rat adrenocorticotropin response to stressors". Endocrinology. 144 (6): 2396–2403. doi: 10.1210/en.2002-0117 . PMID   12746300.
  5. ↑ Wang L, Million M, Rivier J, Rivier C, Craft N, Stenzel-Poore MP, et al. (February 2011). Polymenis M (ed.). "CRF receptor antagonist astressin-B reverses and prevents alopecia in CRF over-expressing mice". PLOS ONE. 6 (2): e16377. Bibcode:2011PLoSO...616377W. doi: 10.1371/journal.pone.0016377 . PMC   3040186 . PMID   21359208.
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