Urodilatin

Last updated
Urodilatin
Urodilatin - Compound Summary (CID 16133394).svg
Urodilatin CDDANP-95-126.gif
Identifiers
  • 118812-69-4 Yes check.svgY
3D model (JSmol)
ChemSpider
KEGG
MeSH Urodilatin
PubChem CID
UNII
  • InChI=1S/C145H234N52O44S3/c1-11-72(6)112-137(238)171-60-106(208)172-73(7)113(214)177-86(40-41-103(146)205)122(223)190-95(63-198)116(217)170-61-108(210)175-88(51-70(2)3)114(215)169-62-109(211)176-100(133(234)187-92(56-104(147)206)127(228)193-97(65-200)130(231)186-91(54-77-27-16-13-17-28-77)126(227)180-82(31-20-45-163-142(153)154)119(220)189-94(139(240)241)55-78-36-38-79(204)39-37-78)68-243-244-69-101(134(235)185-90(53-76-25-14-12-15-26-76)115(216)168-58-105(207)167-59-107(209)174-80(29-18-43-161-140(149)150)117(218)182-87(42-50-242-10)123(224)188-93(57-110(212)213)128(229)181-85(124(225)196-112)34-23-48-166-145(159)160)195-132(233)99(67-202)194-131(232)98(66-201)192-120(221)83(32-21-46-164-143(155)156)178-118(219)81(30-19-44-162-141(151)152)179-125(226)89(52-71(4)5)184-129(230)96(64-199)191-121(222)84(33-22-47-165-144(157)158)183-135(236)102-35-24-49-197(102)138(239)74(8)173-136(237)111(148)75(9)203/h12-17,25-28,36-39,70-75,80-102,111-112,198-204H,11,18-24,29-35,40-69,148H2,1-10H3,(H2,146,205)(H2,147,206)(H,167,207)(H,168,216)(H,169,215)(H,170,217)(H,171,238)(H,172,208)(H,173,237)(H,174,209)(H,175,210)(H,176,211)(H,177,214)(H,178,219)(H,179,226)(H,180,227)(H,181,229)(H,182,218)(H,183,236)(H,184,230)(H,185,235)(H,186,231)(H,187,234)(H,188,224)(H,189,220)(H,190,223)(H,191,222)(H,192,221)(H,193,228)(H,194,232)(H,195,233)(H,196,225)(H,212,213)(H,240,241)(H4,149,150,161)(H4,151,152,162)(H4,153,154,163)(H4,155,156,164)(H4,157,158,165)(H4,159,160,166)/t72-,73-,74-,75+,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,111-,112-/m0/s1
  • CCC(C)C1C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NCC(=O)NC(C(=O)NCC(=O)NC(CSSCC(C(=O)NC(C(=O)NCC(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)N1)CCCNC(=N)N)CC(=O)O)CCSC)CCCNC(=N)N)Cc2ccccc2)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCCNC(=N)N)NC(=O)C(CC(C)C)NC(=O)C(CO)NC(=O)C(CCCNC(=N)N)NC(=O)C3CCCN3C(=O)C(C)NC(=O)C(C(C)O)N)C(=O)NC(CC(=O)N)C(=O)NC(CO)C(=O)NC(Cc4ccccc4)C(=O)NC(CCCNC(=N)N)C(=O)NC(Cc5ccc(cc5)O)C(=O)O)CC(C)C)CO)CCC(=O)N)C
Properties
C145H234N52O44S3
Molar mass 3505.926
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Urodilatin (URO) is a hormone that causes natriuresis by increasing renal blood flow. It is secreted in response to increased mean arterial pressure and increased blood volume from the cells of the distal tubule and collecting duct. It is important in oliguric patients (such as those with acute kidney injury and chronic kidney failure) as it lowers serum creatinine and increases urine output.

Interactions

Atrial natriuretic peptide (CDD/ANP-99-126) [1] is a hormone system of clinical importance. Urodilatin (CDD/ ANP-95-126) is a homologue natriuretic peptide that differs from CDD/ANP-99-126, which is excreted into the circulation via exocytosis. The prototype of the natriuretic hormones is cardiodilatin / atrial natriuretic peptide (CDD/ANP). [2] The endocrine heart is composed of specific myoendocrine cells that synthesize and secrete the natriuretic peptide hormones, which exhibit diuretic and vasorelaxant properties; secretion is the basis for a paracrine system regulating water and sodium reabsorption. [3]

Research efforts since the early 1980s have studied their effects on electrolyte homeostasis. [4] When administered intravenously, urodilatin induces strong diuresis and natriuresis with tolerable hemodynamic side effects. [5] Urodilatin is localized in the kidney, differentially processed (involved in the regulation of body fluid volume and water-electrolyte excretion, while circulating), and secreted into the urine. [5] As a consequence, urodilatin is involved in drug development along with the prohormone CDD/ANP-1-126 [2] and cardiodilatin CDD/ANP-99-126. [3] A message for the preprohormone is transcribed in the heart and kidneys from the gene of NP type A, resulting in a cGMP-dependent signal transduction, which induces diuresis and natriuresis, [6] differentially processed to a peptide of 32 amino acids from the same precursor as renal ANP, may not be identical to the circulating cardiac hormone ANP. [7] The kidneys produce their own natriuretic 32-residue peptide. Urodilatin renal natriuretic peptide potency equals or exceeds that of Atriopeptin [ANP-(99-126)], the prototype of cardiodilatin. [8] Atriopeptin is only of trivial importance in the regulation of sodium excretion during normal living conditions. [9]

Urodilatin is little affected by renal enzymes that inactivate atriopeptin, as the kidney elutes with urodilatin rather than with ANP. [10] The degradation rates of (125I)-urodilatin and [125I]-ANP by pure recombinant NEP (rNEP) were compared. Phosphoramidon, a potent inhibitor of NEP, completely protected both peptides from metabolism by rNEP. [11] Urodilatin has a four-residue extension at the N-terminus neutral endopeptidase-24.11 (NEP) plays a physiological role in metabolizing atrial natriuretic peptide, and C-type natriuretic peptide (prohormone) degraded the bioactive peptides at about half the rate though the C-terminal that compete with natriuretic peptides for hydrolysis by neutral endopeptidase. [12]

Related Research Articles

Vasopressin Mammalian hormone released from the pituitary gland

Vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon of that cell, which terminates in the posterior pituitary, and is released from vesicles into the circulation in response to extracellular fluid hypertonicity (hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the circulation from the filtrate in the kidney tubules of the nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure.

Renin–angiotensin system

The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure and fluid and electrolyte balance, as well as systemic vascular resistance.

Atrial natriuretic peptide Cardiac hormone which increases renal sodium excretion

Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides are a family of hormone/paracrine factors that are structurally related. The main function of ANP is causing a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion. ANP is synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart. These cells contain volume receptors which respond to increased stretching of the atrial wall due to increased atrial blood volume.

Renal physiology Study of the physiology of the kidney

Renal physiology is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, and other electrolytes; clearance of toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by excessive unsuppressible release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH causes an unrelenting increase in solute-free water being returned by the tubules of the kidney to the venous circulation.

Natriuresis is the process of sodium excretion in the urine through the action of the kidneys. It is promoted by ventricular and atrial natriuretic peptides as well as calcitonin, and inhibited by chemicals such as aldosterone. Natriuresis lowers the concentration of sodium in the blood and also tends to lower blood volume because osmotic forces drag water out of the body's blood circulation and into the urine along with the sodium. Many diuretic drugs take advantage of this mechanism to treat medical conditions like hypernatremia and hypertension, which involve excess blood volume.

An atrial natriuretic peptide receptor is a receptor for atrial natriuretic peptide.

A natriuretic peptide is a peptide that induces natriuresis, which is the excretion of sodium by the kidneys.

Neprilysin

Neprilysin, also known as membrane metallo-endopeptidase (MME), neutral endopeptidase (NEP), cluster of differentiation 10 (CD10), and common acute lymphoblastic leukemia antigen (CALLA) is an enzyme that in humans is encoded by the MME gene. Neprilysin is a zinc-dependent metalloprotease that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin. It also degrades the amyloid beta peptide whose abnormal folding and aggregation in neural tissue has been implicated as a cause of Alzheimer's disease. Synthesized as a membrane-bound protein, the neprilysin ectodomain is released into the extracellular domain after it has been transported from the Golgi apparatus to the cell surface.

Omapatrilat

Omapatrilat is an experimental antihypertensive agent that was never marketed. It inhibits both neprilysin and angiotensin-converting enzyme (ACE). NEP inhibition results in elevated natriuretic peptide levels, promoting natriuresis, diuresis, vasodilation, and reductions in preload and ventricular remodeling.

Natriuretic peptide precursor C

Natriuretic peptide precursor C, also known as NPPC, is a protein that in humans is encoded by the NPPC gene. The precursor NPPC protein is cleaved to the 22 amino acid peptide C-type natriuretic peptide (CNP).

NPR1

Natriuretic peptide receptor A/guanylate cyclase A , also known as NPR1, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR1 gene.

NPR3

Natriuretic peptide receptor C/guanylate cyclase C , also known as NPR3, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR3 gene.

CORIN

Corin, also called atrial natriuretic peptide-converting enzyme, is a protein that in humans is encoded by the CORIN gene.

Adolfo José de Bold was an Argentinian-Canadian cardiovascular researcher, best known for his discovery of atrial natriuretic peptide (ANP), a polypeptide hormone secreted by heart muscle cells. The hormone plays a role in regulating blood pressure, blood volume, and cardiovascular growth, and its discovery proved the endocrine function of the heart.

Candoxatril Chemical compound

Candoxatril is the orally active prodrug of candoxatrilat (UK-73967) human neutral endopeptidase (Neprilysin) as the neutral endopeptidase 24.11 complexed (RB-101) with phosphoramidon degrades and inactivates a number of bioactive peptides. Two multiply connected folding domains of the neutral endopeptidase locus splicing of exons 1, 2a, or 2b to the common exon 3 composed of 24 exons of the human CALLA/NEP gene containing the active site, it is known as peptidase family M13 the gluzincins a faint but significant structural relationship of the metzincins to the thermolysin-like enzymes, Zincin is the simplest descriptor of biological space. The structure reveals two multiply connected folding domains which embrace a large central cavity containing the active site of the 5-indanyl ester prodrug candoxatril and differs from phosphoramidon [N-(N- -L- leucyl)-L-tryptophan] in several respects the structure of human neutral endopeptidase complexed with phosphoramidon is lost due to desolvation of the enzyme and ligand on formation of the complex Candoxatril.

Oligopeptidase

An Oligopeptidase is an enzyme that cleaves peptides but not proteins. This property is due to its structure: the active site of this enzyme is located at the end of a narrow cavity which can only be reached by peptides.

Dactylysin is an enzyme. This enzyme catalyses the following chemical reaction

Ventricular natriuretic peptide

Ventricular natriuretic peptide or brain natriuretic peptide (BNP), also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume.

Anaritide Synthetic Peptide

Anaritide is a synthetic analogue of atrial natriuretic peptide (ANP).

References

  1. ↑ Gagelmann M, Hock D, Forssmann WG (June 1988). "Urodilatin (CDD/ANP-95-126) is not biologically inactivated by a peptidase from dog kidney cortex membranes in contrast to atrial natriuretic peptide/cardiodilatin (alpha-hANP/CDD-99-126)". FEBS Lett. 233 (2): 249–54. doi:10.1016/0014-5793(88)80436-8. PMID   2968281. S2CID   28895937.
  2. 1 2 Meyer M, Stief CG, Becker AJ, Truss MC, Taher A, Jonas U, Forssmann WG (June 1988). "The renal paracrine peptide system--possible urologic implications of urodilatin". World J Urol. 14 (2): 249–54. doi:10.1007/BF00183118. ISSN   0724-4983. PMID   8986039. S2CID   37318078.
  3. 1 2 Forssmann WG, Richter R, Meyer M (October 1998). "The endocrine heart and natriuretic peptides: histochemistry, cell biology, and functional aspects of the renal urodilatin system". Histochem Cell Biol. 110 (4): 335–57. doi:10.1007/s004180050295. PMID   9792413. S2CID   9324731.
  4. ↑ Meyer M, Schulz-Knappe P, Kuse ER, Hummel M, Hetzer R, Pichlmayr R, Forssmann WG (February 1995). "[Urodilatin. Use of a new peptide in intensive care]". Anaesthesist. 44 (2): 81–91. doi:10.1007/s001010050135. PMID   7702187. S2CID   5706848.
  5. 1 2 Kuse ER, Meyer M, Constantin R, Oldhafer K, Schlitt HJ, Schulz-Knappe P, Uberbacher HJ, Pichlmayr R, Forssmann WG (April 1996). "[Urodilatin (INN: ularitide). A new peptide in the treatment of acute kidney failure following liver transplantation]". Anaesthesist. 45 (4): 351–8. doi:10.1007/s001010050271. PMID   8702053. S2CID   34683941.
  6. ↑ Meyer M, Richter R, Forssmann WG (October 1998). "Urodilatin, a natriuretic peptide with clinical implications". Eur J Med Res. 3 (1–2): 103–110. PMID   9512977.
  7. ↑ Forssmann W, Meyer M, Forssmann K (August 2001). "The renal urodilatin system: clinical implications". Cardiovasc. Res. 51 (3): 450–62. doi: 10.1016/S0008-6363(01)00331-5 . PMID   11476735.
  8. ↑ Goetz KL. (December 1991). "Renal natriuretic peptide (urodilatin?) and atriopeptin: evolving concepts". Am J Physiol. 261 (6): 921–32. doi:10.1152/ajprenal.1991.261.6.F921. PMID   1836308.
  9. ↑ Goetz KL. (December 1993). "Is urodilatin (rather than atriopeptin) the primary natriuretic peptide of the ANP family?". J Cardiovasc Pharmacol. 22 (6): 911–913. doi:10.1097/00005344-199322002-00027. PMID   7508039.
  10. ↑ Goetz K, Drummer C, Zhu JL, Leadley R, Fiedler F, Gerzer R (December 1990). "Evidence that urodilatin, rather than ANP, regulates renal sodium excretion". J Am Soc Nephrol. 1 (6): 867–74. doi:10.1681/ASN.V16867. ISSN   1533-3450. PMID   1966524.
  11. ↑ Abassi ZA, Golomb E, Agbaria R, Roller PP, Tate J, Keiser HR (September 1994). "Hydrolysis of iodine labelled urodilatin and ANP by recombinant neutral endopeptidase EC. 3.4.24.11". Br J Pharmacol. 113 (1): 204–208. doi:10.1111/j.1476-5381.1994.tb16194.x. PMC   1510039 . PMID   7812611.
  12. ↑ Kenny AJ, Bourne A, Ingram J (April 1998). "Hydrolysis of human and pig brain natriuretic peptides, urodilatin, C-type natriuretic peptide and some C-receptor ligands by endopeptidase-24.11". Biochem. J. 1 (291): 83–8. doi:10.1042/bj2910083. PMC   1132484 . PMID   8097089.
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