KEGG   PATHWAY: rno04924
Entry
rno04924                    Pathway                                

Name
Renin secretion - Rattus norvegicus (rat)
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
rno04924  Renin secretion
rno04924

Other DBs
GO: 0002001
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
24925  Adrb1; beta-1 adrenergic receptor [KO:K04141]
24176  Adrb2; beta-2 adrenergic receptor [KO:K04142]
25645  Adrb3; beta-3 adrenergic receptor [KO:K04143]
24166  Adcyap1; pituitary adenylate cyclase-activating polypeptide precursor [KO:K05262]
24167  Adcyap1r1; pituitary adenylate cyclase-activating polypeptide type I receptor isoform a precursor [KO:K04587]
25240  Aqp1; aquaporin-1 [KO:K09864]
81752  Ptger2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
84023  Ptger4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
81646  Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
83731  Kcnma1; calcium-activated potassium channel subunit alpha-1 [KO:K04936]
81529  Pde1a; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A [KO:K13755] [EC:3.1.4.17]
29691  Pde1b; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B [KO:K13755] [EC:3.1.4.17]
81742  Pde1c; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C [KO:K13755] [EC:3.1.4.17]
50678  Pde3a; cGMP-inhibited 3',5'-cyclic phosphodiesterase A [KO:K19021] [EC:3.1.4.17]
29516  Pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
24715  Ren; renin precursor [KO:K01380] [EC:3.4.23.15]
29290  Adora1; adenosine receptor A1 [KO:K04265]
25686  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
25643  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
81664  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
304496  Orai1; calcium release-activated calcium channel protein 1 [KO:K16056]
308015  Clca1; calcium-activated chloride channel regulator 1 precursor [KO:K05027]
308016  Clca2; calcium-activated chloride channel regulator 2 [KO:K05028]
362053  Clca4; calcium-activated chloride channel regulator 4 precursor [KO:K05030]
499721  Clca4l; chloride channel calcium activated 4-like precursor [KO:K05030]
362052  Clca5; chloride channel accessory 5 precursor [KO:K05030]
24239  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
29716  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
114493  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
682930  Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
29712  Kcnj2; inward rectifier potassium channel 2 [KO:K04996]
24323  Edn1; endothelin-1 preproprotein [KO:K16366]
24324  Edn2; endothelin-2 precursor [KO:K16367]
366270  Edn3; endothelin-3 precursor [KO:K05227]
24326  Ednra; endothelin-1 receptor precursor [KO:K04197]
24180  Agtr1a; type-1A angiotensin II receptor [KO:K04166]
81638  Agtr1b; type-1B angiotensin II receptor [KO:K04166]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
50663  Calm2; calmodulin-2 [KO:K02183]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
24674  Ppp3ca; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
29748  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
29749  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
66012  Gucy1a2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
497757  Gucy1a1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
25206  Gucy1b2; guanylate cyclase soluble subunit beta-2 isoform 2 [KO:K12319] [EC:4.6.1.2]
25202  Gucy1b1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
24602  Nppa; natriuretic peptides A precursor [KO:K12334]
24603  Npr1; atrial natriuretic peptide receptor 1 precursor [KO:K12323] [EC:4.6.1.2]
25523  Prkg2; cGMP-dependent protein kinase 2 [KO:K19477] [EC:2.7.11.12]
64529  Ctsb; cathepsin B preproprotein [KO:K01363] [EC:3.4.22.1]
24179  Agt; angiotensinogen precursor [KO:K09821]
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]
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
  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
  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
  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
  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
  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
  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
  Authors
Persson PB
  Title
Renin: origin, secretion and synthesis.
  Journal
J Physiol 552:667-71 (2003)
DOI:10.1113/jphysiol.2003.049890
Reference
  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
  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
  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
  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
  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
  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
rno04020  Calcium signaling pathway
rno04022  cGMP-PKG signaling pathway
rno04024  cAMP signaling pathway
rno04614  Renin-angiotensin system
KO pathway
ko04924   

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