KEGG   PATHWAY: hsa04924
hsa04924                    Pathway                                

Renin secretion - Homo sapiens (human)
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.
Organismal Systems; Endocrine system
Pathway map
hsa04924  Renin secretion

D00150  Angiotensin II (INN)
D00624  Perindopril erbumine (JAN/USP)
D02014  Angiotensin II (USAN)
D02939  Angiotensin amide (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)
D11142  Angiotensin II acetate (USAN)
D11580  Perindopril arginine
D11664  Clazosentan (USAN/INN)
Other DBs
GO: 0002001
Homo sapiens (human) [GN:hsa]
153  ADRB1; adrenoceptor beta 1 [KO:K04141]
154  ADRB2; adrenoceptor beta 2 [KO:K04142]
155  ADRB3; adrenoceptor beta 3 [KO:K04143]
116  ADCYAP1; adenylate cyclase activating polypeptide 1 [KO:K05262]
117  ADCYAP1R1; ADCYAP receptor type I [KO:K04587]
358  AQP1; aquaporin 1 (Colton blood group) [KO:K09864]
5732  PTGER2; prostaglandin E receptor 2 [KO:K04259]
5734  PTGER4; prostaglandin E receptor 4 [KO:K04261]
2778  GNAS; GNAS complex locus [KO:K04632]
111  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:]
112  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:]
1385  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
3778  KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936]
5136  PDE1A; phosphodiesterase 1A [KO:K13755] [EC:]
5153  PDE1B; phosphodiesterase 1B [KO:K13755] [EC:]
5137  PDE1C; phosphodiesterase 1C [KO:K13755] [EC:]
5139  PDE3A; phosphodiesterase 3A [KO:K19021] [EC:]
5140  PDE3B; phosphodiesterase 3B [KO:K13296] [EC:]
5972  REN; renin [KO:K01380] [EC:]
134  ADORA1; adenosine A1 receptor [KO:K04265]
2770  GNAI1; G protein subunit alpha i1 [KO:K04630]
2773  GNAI3; G protein subunit alpha i3 [KO:K04630]
2771  GNAI2; G protein subunit alpha i2 [KO:K04630]
84876  ORAI1; ORAI calcium release-activated calcium modulator 1 [KO:K16056]
1179  CLCA1; chloride channel accessory 1 [KO:K05027]
9635  CLCA2; chloride channel accessory 2 [KO:K05028]
22802  CLCA4; chloride channel accessory 4 [KO:K05030]
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]
3759  KCNJ2; potassium inwardly rectifying channel subfamily J member 2 [KO:K04996]
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]
185  AGTR1; angiotensin II receptor type 1 [KO:K04166]
2776  GNAQ; G protein subunit alpha q [KO:K04634]
23236  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:]
5330  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:]
5331  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:]
5332  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:]
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]
810  CALML3; calmodulin like 3 [KO:K02183]
805  CALM2; calmodulin 2 [KO:K02183]
808  CALM3; calmodulin 3 [KO:K02183]
801  CALM1; calmodulin 1 [KO:K02183]
163688  CALML6; calmodulin like 6 [KO:K02183]
51806  CALML5; calmodulin like 5 [KO:K02183]
91860  CALML4; calmodulin like 4 [KO:K02183]
5530  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:]
5532  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:]
5533  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:]
5534  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
5535  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
2977  GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:]
2982  GUCY1A1; guanylate cyclase 1 soluble subunit alpha 1 [KO:K12318] [EC:]
2983  GUCY1B1; guanylate cyclase 1 soluble subunit beta 1 [KO:K12319] [EC:]
4878  NPPA; natriuretic peptide A [KO:K12334]
4881  NPR1; natriuretic peptide receptor 1 [KO:K12323] [EC:]
5593  PRKG2; protein kinase cGMP-dependent 2 [KO:K19477] [EC:]
1508  CTSB; cathepsin B [KO:K01363] [EC:]
183  AGT; angiotensinogen [KO:K09821]
1636  ACE; angiotensin I converting enzyme [KO:K01283] [EC:]
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
Kurtz A
Renin release: sites, mechanisms, and control.
Annu Rev Physiol 73:377-99 (2011)
Schweda F, Friis U, Wagner C, Skott O, Kurtz A
Renin release.
Physiology (Bethesda) 22:310-9 (2007)
Castrop H, Hocherl K, Kurtz A, Schweda F, Todorov V, Wagner C
Physiology of kidney renin.
Physiol Rev 90:607-73 (2010)
Friis UG, Madsen K, Stubbe J, Hansen PB, Svenningsen P, Bie P, Skott O, Jensen BL
Regulation of renin secretion by renal juxtaglomerular cells.
Pflugers Arch 465:25-37 (2013)
Kim SM, Briggs JP, Schnermann J
Convergence of major physiological stimuli for renin release on the Gs-alpha/cyclic adenosine monophosphate signaling pathway.
Clin Exp Nephrol 16:17-24 (2012)
Kurtz A
Control of renin synthesis and secretion.
Am J Hypertens 25:839-47 (2012)
Kurtz A, Wagner C
Cellular control of renin secretion.
J Exp Biol 202:219-25 (1999)
Persson PB
Renin: origin, secretion and synthesis.
J Physiol 552:667-71 (2003)
Schweda F, Kurtz A
Cellular mechanism of renin release.
Acta Physiol Scand 181:383-90 (2004)
Sparks MA, Crowley SD, Gurley SB, Mirotsou M, Coffman TM
Classical Renin-Angiotensin system in kidney physiology.
Compr Physiol 4:1201-28 (2014)
Harrison-Bernard LM
The renal renin-angiotensin system.
Adv Physiol Educ 33:270-4 (2009)
Schnermann J, Briggs JP
Synthesis and secretion of renin in mice with induced genetic mutations.
Kidney Int 81:529-38 (2012)
Ryan MJ, Black TA, Millard SL, Gross KW, Hajduczok G
Endothelin-1 increases calcium and attenuates renin gene expression in As4.1 cells.
Am J Physiol Heart Circ Physiol 283:H2458-65 (2002)
Hautmann M, Friis UG, Desch M, Todorov V, Castrop H, Segerer F, Otto C, Schutz G, Schweda F
Pituitary adenylate cyclase-activating polypeptide stimulates renin secretion via activation of PAC1 receptors.
J Am Soc Nephrol 18:1150-6 (2007)
hsa04020  Calcium signaling pathway
hsa04022  cGMP-PKG signaling pathway
hsa04024  cAMP signaling pathway
hsa04614  Renin-angiotensin system
KO pathway

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