KEGG   PATHWAY: hsa04924
Entry
hsa04924                    Pathway                                
Name
Renin secretion - Homo sapiens (human)
Description
The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in extracellular fluid volume and blood pressure homeostasis of the body. Renin is synthesized, stored in, and released into circulation by the juxtaglomerular (JG) cells of the kidney. Secretion of renin from JG cells at the organ level is controlled by the four main mechanisms: the sympathetic nervous system, the local JG apparatus baroreflex, the macula densa mechanism, and several hormones acting locally within the JG apparatus. Renin secretion at the level of renal JG cells appears to be controlled mainly by classic second messengers, namely cAMP, cGMP, and free cytosolic calcium concentration. While cAMP generally stimulates renin release and the intracellular calcium concentration suppresses the exocytosis of renin, the effects of cGMP in the regulation of the renin system are more complex as it both may stimulate or inhibit renin release.
Class
Organismal Systems; Endocrine system
Pathway map
hsa04924  Renin secretion
hsa04924

Drug
D00150  Angiotensin II (INN)
D00624  Perindopril erbumine (JAN/USP)
D02014  Angiotensin II (USAN)
D02939  Angiotensin amide (USAN)
D03009  Atrasentan hydrochloride (USAN)
D03605  Crofelemer (USAN)
D03753  Perindopril (USAN/INN)
D04312  Gemopatrilat (USAN/INN)
D05801  Saprisartan potassium (USAN)
D05818  Selodenoson (USAN/INN)
D05879  Solabegron hydrochloride (USAN)
D06076  Teprotide (USAN/INN)
D07682  Clazosentan sodium (JAN/USAN)
D11142  Angiotensin II acetate (USAN)
D11580  Perindopril arginine
D11664  Clazosentan (USAN/INN)
D12840  Zilebesiran sodium (JAN/USAN)
Other DBs
GO: 0002001
Organism
Homo sapiens (human) [GN:hsa]
Gene
111  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
116  ADCYAP1; adenylate cyclase activating polypeptide 1 [KO:K05262]
117  ADCYAP1R1; ADCYAP receptor type I [KO:K04587]
1179  CLCA1; chloride channel accessory 1 [KO:K05027]
134  ADORA1; adenosine A1 receptor [KO:K04265]
1385  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
1508  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
153  ADRB1; adrenoceptor beta 1 [KO:K04141]
154  ADRB2; adrenoceptor beta 2 [KO:K04142]
155  ADRB3; adrenoceptor beta 3 [KO:K04143]
1636  ACE; angiotensin I converting enzyme [KO:K01283] [EC:3.4.15.1]
163688  CALML6; calmodulin like 6 [KO:K02183]
183  AGT; angiotensinogen [KO:K09821]
185  AGTR1; angiotensin II receptor type 1 [KO:K04166]
1906  EDN1; endothelin 1 [KO:K16366]
1907  EDN2; endothelin 2 [KO:K16367]
1908  EDN3; endothelin 3 [KO:K05227]
1909  EDNRA; endothelin receptor type A [KO:K04197]
22802  CLCA4; chloride channel accessory 4 [KO:K05030]
23236  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
2770  GNAI1; G protein subunit alpha i1 [KO:K04630]
2771  GNAI2; G protein subunit alpha i2 [KO:K04630]
2773  GNAI3; G protein subunit alpha i3 [KO:K04630]
2776  GNAQ; G protein subunit alpha q [KO:K04634]
2778  GNAS; GNAS complex locus [KO:K04632]
2977  GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:4.6.1.2]
2982  GUCY1A1; guanylate cyclase 1 soluble subunit alpha 1 [KO:K12318] [EC:4.6.1.2]
2983  GUCY1B1; guanylate cyclase 1 soluble subunit beta 1 [KO:K12319] [EC:4.6.1.2]
358  AQP1; aquaporin 1 (Colton blood group) [KO:K09864]
3708  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
3709  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
3710  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
3759  KCNJ2; potassium inwardly rectifying channel subfamily J member 2 [KO:K04996]
3778  KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936]
4878  NPPA; natriuretic peptide A [KO:K12334]
4881  NPR1; natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
5136  PDE1A; phosphodiesterase 1A [KO:K13755] [EC:3.1.4.17]
5137  PDE1C; phosphodiesterase 1C [KO:K13755] [EC:3.1.4.17]
5139  PDE3A; phosphodiesterase 3A [KO:K19021] [EC:3.1.4.17]
5140  PDE3B; phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
5153  PDE1B; phosphodiesterase 1B [KO:K13755] [EC:3.1.4.17]
51806  CALML5; calmodulin like 5 [KO:K02183]
5330  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
5331  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
5332  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
5530  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
5532  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
5533  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
5534  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
5535  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
5593  PRKG2; protein kinase cGMP-dependent 2 [KO:K19477] [EC:2.7.11.12]
5732  PTGER2; prostaglandin E receptor 2 [KO:K04259]
5734  PTGER4; prostaglandin E receptor 4 [KO:K04261]
5972  REN; renin [KO:K01380] [EC:3.4.23.15]
775  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
776  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
778  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
779  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
801  CALM1; calmodulin 1 [KO:K02183]
805  CALM2; calmodulin 2 [KO:K02183]
808  CALM3; calmodulin 3 [KO:K02183]
810  CALML3; calmodulin like 3 [KO:K02183]
84876  ORAI1; ORAI calcium release-activated calcium modulator 1 [KO:K16056]
91860  CALML4; calmodulin like 4 [KO:K02183]
9635  CLCA2; chloride channel accessory 2 [KO:K05028]
Compound
C00001  H2O
C00002  ATP
C00008  ADP
C00020  AMP
C00076  Calcium cation
C00212  Adenosine
C00238  Potassium cation
C00533  Nitric oxide
C00547  L-Noradrenaline
C00575  3',5'-Cyclic AMP
C00584  Prostaglandin E2
C00698  Cl-
C00788  L-Adrenaline
C00873  Angiotensin I
C00942  3',5'-Cyclic GMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C02135  Angiotensin II
Reference
PMID:20936939
  Authors
Kurtz A
  Title
Renin release: sites, mechanisms, and control.
  Journal
Annu Rev Physiol 73:377-99 (2011)
DOI:10.1146/annurev-physiol-012110-142238
Reference
PMID:17928544
  Authors
Schweda F, Friis U, Wagner C, Skott O, Kurtz A
  Title
Renin release.
  Journal
Physiology (Bethesda) 22:310-9 (2007)
DOI:10.1152/physiol.00024.2007
Reference
PMID:20393195
  Authors
Castrop H, Hocherl K, Kurtz A, Schweda F, Todorov V, Wagner C
  Title
Physiology of kidney renin.
  Journal
Physiol Rev 90:607-73 (2010)
DOI:10.1152/physrev.00011.2009
Reference
PMID:22733355
  Authors
Friis UG, Madsen K, Stubbe J, Hansen PB, Svenningsen P, Bie P, Skott O, Jensen BL
  Title
Regulation of renin secretion by renal juxtaglomerular cells.
  Journal
Pflugers Arch 465:25-37 (2013)
DOI:10.1007/s00424-012-1126-7
Reference
PMID:22124804
  Authors
Kim SM, Briggs JP, Schnermann J
  Title
Convergence of major physiological stimuli for renin release on the Gs-alpha/cyclic adenosine monophosphate signaling pathway.
  Journal
Clin Exp Nephrol 16:17-24 (2012)
DOI:10.1007/s10157-011-0494-1
Reference
PMID:22237158
  Authors
Kurtz A
  Title
Control of renin synthesis and secretion.
  Journal
Am J Hypertens 25:839-47 (2012)
DOI:10.1038/ajh.2011.246
Reference
PMID:9882634
  Authors
Kurtz A, Wagner C
  Title
Cellular control of renin secretion.
  Journal
J Exp Biol 202:219-25 (1999)
Reference
PMID:12949225
  Authors
Persson PB
  Title
Renin: origin, secretion and synthesis.
  Journal
J Physiol 552:667-71 (2003)
DOI:10.1113/jphysiol.2003.049890
Reference
PMID:15283749
  Authors
Schweda F, Kurtz A
  Title
Cellular mechanism of renin release.
  Journal
Acta Physiol Scand 181:383-90 (2004)
DOI:10.1111/j.1365-201X.2004.01309.x
Reference
PMID:24944035
  Authors
Sparks MA, Crowley SD, Gurley SB, Mirotsou M, Coffman TM
  Title
Classical Renin-Angiotensin system in kidney physiology.
  Journal
Compr Physiol 4:1201-28 (2014)
DOI:10.1002/cphy.c130040
Reference
PMID:19948673
  Authors
Harrison-Bernard LM
  Title
The renal renin-angiotensin system.
  Journal
Adv Physiol Educ 33:270-4 (2009)
DOI:10.1152/advan.00049.2009
Reference
PMID:22258323
  Authors
Schnermann J, Briggs JP
  Title
Synthesis and secretion of renin in mice with induced genetic mutations.
  Journal
Kidney Int 81:529-38 (2012)
DOI:10.1038/ki.2011.451
Reference
PMID:12388321
  Authors
Ryan MJ, Black TA, Millard SL, Gross KW, Hajduczok G
  Title
Endothelin-1 increases calcium and attenuates renin gene expression in As4.1 cells.
  Journal
Am J Physiol Heart Circ Physiol 283:H2458-65 (2002)
DOI:10.1152/ajpheart.00295.2002
Reference
PMID:17360952
  Authors
Hautmann M, Friis UG, Desch M, Todorov V, Castrop H, Segerer F, Otto C, Schutz G, Schweda F
  Title
Pituitary adenylate cyclase-activating polypeptide stimulates renin secretion via activation of PAC1 receptors.
  Journal
J Am Soc Nephrol 18:1150-6 (2007)
DOI:10.1681/ASN.2006060633
Related
pathway
hsa04020  Calcium signaling pathway
hsa04022  cGMP-PKG signaling pathway
hsa04024  cAMP signaling pathway
hsa04614  Renin-angiotensin system
KO pathway
ko04924   

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