KEGG   PATHWAY: rno04614
Entry
rno04614                    Pathway                                
Name
Renin-angiotensin system - Rattus norvegicus (rat)
Description
The renin-angiotensin system (RAS) is a peptidergic system with endocrine characteristics regarding to the regulation of the blood pressure and hydro-electrolytic balance. In the classical RAS, the enzyme renin cleaves its substrate angiotensinogen (Agt) forming the decapeptide angiotensin I that is in turn cleaved by angiotensin-converting enzyme (ACE) to produce the angiotensin II (Ang II), a key player of this system. Ang II activates its AT1 receptor (AT1R), the principal receptor that mediates the majority of the known actions of Ang II in the kidney, including vasoconstriction, renal sodium (Na+) reabsorption, and aldosterone secretion, increasing blood pressure and contributing to the development of hypertension. In addition to (ACE)/Ang II/AT1R and AT2R axis, other signaling pathways in the RAS, such as ACE2/angiotensin-(1-7)/Mas and Ang IV/IRAP, and other active peptide of the RAS, with physiological relevance as Ang III, Ang A and alamandine, are now widely recognized.
Class
Organismal Systems; Endocrine system
Pathway map
rno04614  Renin-angiotensin system
rno04614

Other DBs
GO: 0002003
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
24179  Agt; angiotensinogen precursor [KO:K09821]
24715  Ren; renin precursor [KO:K01380] [EC:3.4.23.15]
24310  Ace; angiotensin-converting enzyme precursor [KO:K01283] [EC:3.4.15.1]
498012  Ace3; angiotensin I converting enzyme (peptidyl-dipeptidase A) 3 precursor [KO:K01283] [EC:3.4.15.1]
25627  Cma1; chymase precursor [KO:K01329] [EC:3.4.21.39]
100360872  Mcpt1l1; mast cell protease 1 preproprotein [KO:K01329] [EC:3.4.21.39]
290257  Ctsg; cathepsin G precursor [KO:K01319] [EC:3.4.21.20]
24523  Klk1; kallikrein 1 precursor [KO:K01325] [EC:3.4.21.35]
24594  Klk1b3; kallikrein 1-related peptidase B3 precursor [KO:K01325] [EC:3.4.21.35]
24841  Klk1c2; tonin precursor [KO:K01325] [EC:3.4.21.35]
292866  Klk1c8; prostatic glandular kallikrein-6 precursor [KO:K01325] [EC:3.4.21.35]
292855  Klk1c12; glandular kallikrein-12, submandibular/renal precursor [KO:K01325] [EC:3.4.21.35]
292858  Klk1c10; glandular kallikrein-10 precursor [KO:K01325] [EC:3.4.21.35]
100361452  Klk1c4; glandular kallikrein-10 isoform X1 [KO:K01325] [EC:3.4.21.35]
292868  Klk1c9; submandibular glandular kallikrein-9 precursor [KO:K01325] [EC:3.4.21.35]
408242  Klk1c6; kallikrein 1-related peptidase C6 precursor [KO:K01325] [EC:3.4.21.35]
292872  Klk1c3; glandular kallikrein-3, submandibular precursor [KO:K01325] [EC:3.4.21.35]
64017  Enpep; glutamyl aminopeptidase [KO:K11141] [EC:3.4.11.7]
81641  Anpep; aminopeptidase N precursor [KO:K11140] [EC:3.4.11.2]
83471  Prep; prolyl endopeptidase [KO:K01322] [EC:3.4.21.26]
302668  Ace2; angiotensin-converting enzyme 2 precursor [KO:K09708] [EC:3.4.17.23]
296370  Ctsa; lysosomal protective protein precursor [KO:K13289] [EC:3.4.16.5]
54242  Cpa3; mast cell carboxypeptidase A precursor [KO:K08780] [EC:3.4.17.1]
24590  Mme; neprilysin [KO:K01389] [EC:3.4.24.11]
64517  Thop1; thimet oligopeptidase [KO:K01392] [EC:3.4.24.15]
117041  Nln; neurolysin, mitochondrial precursor [KO:K01393] [EC:3.4.24.16]
293118  Prcp; lysosomal Pro-X carboxypeptidase precursor [KO:K01285] [EC:3.4.16.2]
25153  Mas1; proto-oncogene Mas [KO:K04303]
293648  Mrgprd; mas-related G-protein coupled receptor member D [KO:K08392]
24180  Agtr1a; type-1 angiotensin II receptor A [KO:K04166]
81638  Agtr1b; type-1 angiotensin II receptor B [KO:K04166]
24182  Agtr2; type-2 angiotensin II receptor [KO:K04167]
171105  Lnpep; leucyl-cystinyl aminopeptidase [KO:K01257] [EC:3.4.11.3]
302526  Atp6ap2; renin receptor precursor [KO:K19514]
Compound
C00873  Angiotensin I
C02135  Angiotensin II
C15848  Angiotensin III
C15849  Angiotensin IV
C15850  Angiotensin (1-7)
C15851  Angiotensin (1-9)
C15852  Angiotensin (1-5)
C20970  Angiotensin A
C20971  Alamandine
C20972  Angiotensin (5-8)
C20973  Angiotensin (5-7)
Reference
  Authors
Kramkowski K, Mogielnicki A, Buczko W.
  Title
The physiological significance of the alternative pathways of angiotensin II production.
  Journal
J Physiol Pharmacol 57:529-39 (2006)
Reference
  Authors
Danilczyk U, Eriksson U, Oudit GY, Penninger JM.
  Title
Physiological roles of angiotensin-converting enzyme 2.
  Journal
Cell Mol Life Sci 61:2714-9 (2004)
DOI:10.1007/s00018-004-4241-6
Reference
  Authors
Warner FJ, Smith AI, Hooper NM, Turner AJ.
  Title
Angiotensin-converting enzyme-2: a molecular and cellular perspective.
  Journal
Cell Mol Life Sci 61:2704-13 (2004)
DOI:10.1007/s00018-004-4240-7
Reference
  Authors
Kurdi M, De Mello WC, Booz GW.
  Title
Working outside the system: an update on the unconventional behavior of the renin-angiotensin system components.
  Journal
Int J Biochem Cell Biol 37:1357-67 (2005)
DOI:10.1016/j.biocel.2005.01.012
Reference
  Authors
Burrell LM, Johnston CI, Tikellis C, Cooper ME.
  Title
ACE2, a new regulator of the renin-angiotensin system.
  Journal
Trends Endocrinol Metab 15:166-9 (2004)
DOI:10.1016/j.tem.2004.03.001
Reference
  Authors
von Bohlen und Halbach O, Albrecht D.
  Title
The CNS renin-angiotensin system.
  Journal
Cell Tissue Res 326:599-616 (2006)
DOI:10.1007/s00441-006-0190-8
Reference
  Authors
Schmaier AH
  Title
The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction.
  Journal
Am J Physiol Regul Integr Comp Physiol 285:R1-13 (2003)
DOI:10.1152/ajpregu.00535.2002
Reference
  Authors
Eriksson U, Danilczyk U, Penninger JM.
  Title
Just the beginning: novel functions for angiotensin-converting enzymes.
  Journal
Curr Biol 12:R745-52 (2002)
DOI:10.1016/S0960-9822(02)01255-1
Reference
  Authors
Dielis AW, Smid M, Spronk HM, Hamulyak K, Kroon AA, ten Cate H, de Leeuw PW.
  Title
The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikrein-kinin systems.
  Journal
Hypertension 46:1236-42 (2005)
DOI:10.1161/01.HYP.0000193538.20705.23
Reference
  Authors
Kuba K, Imai Y, Penninger JM.
  Title
Angiotensin-converting enzyme 2 in lung diseases.
  Journal
Curr Opin Pharmacol 6:271-6 (2006)
DOI:10.1016/j.coph.2006.03.001
Reference
  Authors
Erdos EG, Jackman HL, Brovkovych V, Tan F, Deddish PA.
  Title
Products of angiotensin I hydrolysis by human cardiac enzymes potentiate bradykinin.
  Journal
J Mol Cell Cardiol 34:1569-76 (2002)
DOI:10.1006/jmcc.2002.2080
Reference
  Authors
Shrimpton CN, Smith AI, Lew RA.
  Title
Soluble metalloendopeptidases and neuroendocrine signaling.
  Journal
Endocr Rev 23:647-64 (2002)
DOI:10.1210/er.2001-0032
Reference
  Authors
Jackman HL, Massad MG, Sekosan M, Tan F, Brovkovych V, Marcic BM, Erdos EG.
  Title
Angiotensin 1-9 and 1-7 release in human heart: role of cathepsin A.
  Journal
Hypertension 39:976-81 (2002)
DOI:10.1161/01.HYP.0000017283.67962.02
Reference
  Authors
Lundequist A, Tchougounova E, Abrink M, Pejler G.
  Title
Cooperation between mast cell carboxypeptidase A and the chymase mouse mast cell protease 4 in the formation and degradation of angiotensin II.
  Journal
J Biol Chem 279:32339-44 (2004)
DOI:10.1074/jbc.M405576200
Reference
  Authors
Kehoe PG, Wilcock GK.
  Title
Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer's disease?
  Journal
Lancet Neurol 6:373-8 (2007)
DOI:10.1016/S1474-4422(07)70077-7
Reference
  Authors
Ferrao FM, Lara LS, Lowe J
  Title
Renin-angiotensin system in the kidney: What is new?
  Journal
World J Nephrol 3:64-76 (2014)
DOI:10.5527/wjn.v3.i3.64
Reference
  Authors
Zhuo JL, Ferrao FM, Zheng Y, Li XC
  Title
New frontiers in the intrarenal Renin-Angiotensin system: a critical review of classical and new paradigms.
  Journal
Front Endocrinol (Lausanne) 4:166 (2013)
DOI:10.3389/fendo.2013.00166
Reference
  Authors
Unger T, Paulis L, Sica DA
  Title
Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches.
  Journal
Eur Heart J 32:2739-47 (2011)
DOI:10.1093/eurheartj/ehr253
Reference
  Authors
Fyhrquist F, Saijonmaa O
  Title
Renin-angiotensin system revisited.
  Journal
J Intern Med 264:224-36 (2008)
DOI:10.1111/j.1365-2796.2008.01981.x
Reference
  Authors
Yugandhar VG, Clark MA
  Title
Angiotensin III: a physiological relevant peptide of the renin angiotensin system.
  Journal
Peptides 46:26-32 (2013)
DOI:10.1016/j.peptides.2013.04.014
Reference
  Authors
Etelvino GM, Peluso AA, Santos RA
  Title
New components of the renin-angiotensin system: alamandine and the MAS-related G protein-coupled receptor D.
  Journal
Curr Hypertens Rep 16:433 (2014)
DOI:10.1007/s11906-014-0433-0
Related
pathway
rno04270  Vascular smooth muscle contraction
rno04610  Complement and coagulation cascades
rno04924  Renin secretion
rno04925  Aldosterone synthesis and secretion
KO pathway
ko04614   
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