ENTRY       hsa04022                    Pathway
NAME        cGMP-PKG signaling pathway - Homo sapiens (human)
DESCRIPTION Cyclic GMP (cGMP) is the intracellular second messenger that mediates the action of nitric oxide (NO) and natriuretic peptides (NPs), regulating a broad array of physiologic processes. The elevated intracellular cGMP level exerts its physiological action through two forms of cGMP-dependent protein kinase (PKG), cGMP-regulated phosphodiesterases (PDE2, PDE3) and cGMP-gated cation channels, among which PKGs might be the primary mediator. PKG1 isoform-specific activation of established substrates leads to reduction of cytosolic calcium concentration and/or decrease in the sensitivity of myofilaments to Ca2+ (Ca2+-desensitization), resulting in smooth muscle relaxation. In cardiac myocyte, PKG directly phosphorylates a member of the transient potential receptor canonical channel family, TRPC6, suppressing this nonselective ion channel's Ca2+ conductance, G-alpha-q agonist-induced NFAT activation, and myocyte hypertrophic responses. PKG also opens mitochondrial ATP-sensitive K+ (mitoKATP) channels and subsequent release of ROS triggers cardioprotection.
CLASS       Environmental Information Processing; Signal transduction
PATHWAY_MAP hsa04022  cGMP-PKG signaling pathway
DRUG        D00095  Epinephrine (USP/INN)
            D00227  Aminophylline (USP/INN)
            D00231  Inamrinone (USP)
            D00255  Carvedilol (JP18/USP/INN)
            D00281  Clonidine (JAN/USP/INN)
            D00302  Dipyridamole (JP18/USP/INN)
            D00371  Theophylline (JP18)
            D00378  Timolol (USAN)
            D00405  Methyldopa (USP)
            D00417  Milrinone (JAN/USP/INN)
            D00432  Nadolol (JP18/USP/INN)
            D00598  Betaxolol hydrochloride (JP18/USP)
            D00599  Carteolol hydrochloride (JP18/USP)
            D00600  Labetalol hydrochloride (JP18/USP)
            D00603  Timolol maleate (JP18/USP)
            D00604  Clonidine hydrochloride (JP18/USP)
            D00606  Guanfacine hydrochloride (JAN/USP)
            D00610  Terazosin hydrochloride (USP)
            D00631  Bepridil hydrochloride (USAN)
            D00632  Dobutamine hydrochloride (JP18/USP)
            D00634  Bisoprolol fumarate (JP18/USP)
            D00636  Amiodarone hydrochloride (JP18/USP)
            D00680  Methylergonovine maleate (USP)
            D00996  Epinephrine hydrochloride (JAN)
            D01024  Tamsulosin hydrochloride (JP18/USP)
            D01163  Ergonovine maleate (USP)
            D01220  Trapidil (JP18/INN)
            D01238  Bucladesine sodium (JAN)
            D01385  Ibudilast (JP18/INN)
            D01469  Amosulalol hydrochloride (JP18)
            D01573  Etilefrine hydrochloride (JP18)
            D01691  Nipradilol (JAN/INN)
            D01692  Alfuzosin hydrochloride (JAN/USAN)
            D01712  Theophylline sodium acetate (JAN)
            D01771  Proxyphylline (JAN/INN)
            D01810  Nicorandil (JP18/USAN/INN)
            D01830  Arotinolol hydrochloride (JP18)
            D01840  Fasudil hydrochloride (JAN)
            D01896  Cilostazol (JP18/USP/INN)
            D01958  Indenolol hydrochloride (JP18)
            D01965  Silodosin (JP18/INN)
            D02017  Oxtriphylline (USP)
            D02084  Inamrinone ethylenelactate
            D02085  Milrinone lactate
            D02149  Epinephrine bitartrate (JAN/USP)
            D02218  Papaverine hydrochloride (JP18/USP)
            D02229  Sildenafil citrate (JAN/USP)
            D02342  Bisoprolol (JAN/USAN/INN)
            D02731  Vardenafil dihydrochoride (USAN)
            D02774  Adrenalone (USAN/INN)
            D02910  Amiodarone (USAN/INN)
            D02976  Arbutamine hydrochloride (USAN)
            D03051  Bamifylline hydrochloride (USAN)
            D03115  Fasudil hydrochloride hydrate (JAN)
            D03177  Bunolol hydrochloride (USAN)
            D03217  Avanafil (USAN/INN)
            D03260  Vardenafil hydrochloride hydrate (JAN)
            D03328  Carperitide (USAN/INN)
            D03415  Carvedilol phosphate (USAN)
            D03657  Dasantafil (USAN/INN)
            D03879  Dobutamine (USAN/INN)
            D03891  Dopexamine (USAN/INN)
            D03892  Dopexamine hydrochloride (USAN)
            D03898  Doxofylline (USAN/INN)
            D03953  Edonentan (USAN)
            D04004  Enoximone (USAN/INN)
            D04508  Imazodan hydrochloride (USAN)
            D04510  Imciromab pentetate (USAN)
            D04529  Indolidan (USAN/INN)
            D04628  Isomazole hydrochloride (USAN)
            D04710  Levobetaxolol hydrochloride (USAN)
            D04720  Levosimendan (USAN/INN)
            D04751  Lixazinone sulfate (USAN)
            D05087  Moxonidine (USAN/INN)
            D05429  Aminophylline hydrate (JP18)
            D05514  Piroximone (USAN)
            D05688  Racepinephrine (USP/INN)
            D05689  Racepinephrine hydrochloride (USP)
            D05879  Solabegron hydrochloride (USAN)
            D06103  Theophylline (USP)
            D06104  Theophylline sodium glycinate (USP)
            D06562  Bedoradrine sulfate (USAN)
            D06671  Yohimbine hydrochloride (USP)
            D07124  Alfuzosin (INN)
            D07181  Mepindolol (INN)
            D07425  Papaverine (BAN)
            D07439  Papaverine sulfate
            D07451  Amosulalol (INN)
            D07465  Arotinolol (INN)
            D07491  Bamifylline (INN)
            D07520  Bepridil (INN)
            D07526  Betaxolol (INN)
            D07546  Bucladesine (INN)
            D07560  Adrenalone hydrochloride
            D07624  Carteolol (INN)
            D07905  Ergometrine (INN)
            D07906  Ergotamine (INN)
            D07931  Etilefrine (INN)
            D07941  Fasudil (INN)
            D08031  Guanfacine (INN)
            D08078  Indenolol (INN)
            D08106  Labetalol (INN)
            D08205  Methyldopa (INN)
            D08207  Methylergometrine (INN)
            D08482  Rilmenidine (INN)
            D08514  Sildenafil (INN)
            D08560  Tamsulosin (INN)
            D08569  Terazosin (INN)
            D08600  Timolol (INN)
            D08668  Vardenafil (USAN/INN)
            D08685  Yohimbine (DCF)
            D09822  Theosalicin (JAN)
            D09989  Vardenafil hydrochloride (USP)
            D10027  Udenafil (USAN/INN)
            D10971  Piclidenoson (USAN/INN)
            D11030  Netarsudil (USAN/INN)
            D11031  Netarsudil mesylate (USAN)
            D11128  Namodenoson (USAN/INN)
            D11190  Vosoritide (USAN/INN)
            D11320  Vatinoxan (USAN)
            D11321  Vatinoxan hydrochloride (USAN)
            D11585  Terazosin hydrochloride anhydrous
            D11630  Aminophylline dihydrate
            D11743  Ensifentrine (USAN/INN)
            D11776  Sparsentan (USAN/INN)
            D11974  Centhaquine (USAN)
            D11975  Centhaquine citrate (USAN)
            D12265  Mavacamten (USAN/INN)
            D12516  Zagociguat (USAN/INN)
DBLINKS     GO: 0070305
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        185  AGTR1; angiotensin II receptor type 1 [KO:K04166]
            1909  EDNRA; endothelin receptor type A [KO:K04197]
            1910  EDNRB; endothelin receptor type B [KO:K04198]
            148  ADRA1A; adrenoceptor alpha 1A [KO:K04135]
            147  ADRA1B; adrenoceptor alpha 1B [KO:K04136]
            146  ADRA1D; adrenoceptor alpha 1D [KO:K04137]
            150  ADRA2A; adrenoceptor alpha 2A [KO:K04138]
            151  ADRA2B; adrenoceptor alpha 2B [KO:K04139]
            152  ADRA2C; adrenoceptor alpha 2C [KO:K04140]
            2776  GNAQ; G protein subunit alpha q [KO:K04634]
            2767  GNA11; G protein subunit alpha 11 [KO:K04635]
            2768  GNA12; G protein subunit alpha 12 [KO:K04346]
            10672  GNA13; G protein subunit alpha 13 [KO:K04639]
            7225  TRPC6; transient receptor potential cation channel subfamily C member 6 [KO:K04969]
            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]
            4205  MEF2A; myocyte enhancer factor 2A [KO:K09260]
            4207  BORCS8-MEF2B; BORCS8-MEF2B readthrough [KO:K09261]
            100271849  MEF2B; myocyte enhancer factor 2B [KO:K09261]
            4208  MEF2C; myocyte enhancer factor 2C [KO:K04454]
            4209  MEF2D; myocyte enhancer factor 2D [KO:K09262]
            4772  NFATC1; nuclear factor of activated T cells 1 [KO:K04446]
            4773  NFATC2; nuclear factor of activated T cells 2 [KO:K17332]
            4775  NFATC3; nuclear factor of activated T cells 3 [KO:K17333]
            4776  NFATC4; nuclear factor of activated T cells 4 [KO:K17334]
            6722  SRF; serum response factor [KO:K04378]
            2626  GATA4; GATA binding protein 4 [KO:K09183]
            4625  MYH7; myosin heavy chain 7 [KO:K17751]
            4624  MYH6; myosin heavy chain 6 [KO:K17751]
            4879  NPPB; natriuretic peptide B [KO:K12335]
            4878  NPPA; natriuretic peptide A [KO:K12334]
            4881  NPR1; natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
            4880  NPPC; natriuretic peptide C [KO:K12336]
            4882  NPR2; natriuretic peptide receptor 2 [KO:K12324] [EC:4.6.1.2]
            5592  PRKG1; protein kinase cGMP-dependent 1 [KO:K07376] [EC:2.7.11.12]
            5593  PRKG2; protein kinase cGMP-dependent 2 [KO:K19477] [EC:2.7.11.12]
            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]
            3778  KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936]
            157855  KCNU1; potassium calcium-activated channel subfamily U member 1 [KO:K05274]
            3779  KCNMB1; potassium calcium-activated channel subfamily M regulatory beta subunit 1 [KO:K04937]
            10242  KCNMB2; potassium calcium-activated channel subfamily M regulatory beta subunit 2 [KO:K04938]
            27094  KCNMB3; potassium calcium-activated channel subfamily M regulatory beta subunit 3 [KO:K04939]
            27345  KCNMB4; potassium calcium-activated channel subfamily M regulatory beta subunit 4 [KO:K04941]
            6546  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
            6543  SLC8A2; solute carrier family 8 member A2 [KO:K05849]
            6547  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
            476  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:7.2.2.13]
            477  ATP1A2; ATPase Na+/K+ transporting subunit alpha 2 [KO:K01539] [EC:7.2.2.13]
            478  ATP1A3; ATPase Na+/K+ transporting subunit alpha 3 [KO:K01539] [EC:7.2.2.13]
            480  ATP1A4; ATPase Na+/K+ transporting subunit alpha 4 [KO:K01539] [EC:7.2.2.13]
            23439  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
            481  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
            482  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
            483  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
            486  FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
            490  ATP2B1; ATPase plasma membrane Ca2+ transporting 1 [KO:K05850] [EC:7.2.2.10]
            492  ATP2B3; ATPase plasma membrane Ca2+ transporting 3 [KO:K05850] [EC:7.2.2.10]
            493  ATP2B4; ATPase plasma membrane Ca2+ transporting 4 [KO:K05850] [EC:7.2.2.10]
            491  ATP2B2; ATPase plasma membrane Ca2+ transporting 2 [KO:K05850] [EC:7.2.2.10]
            5997  RGS2; regulator of G protein signaling 2 [KO:K18154]
            9569  GTF2IRD1; GTF2I repeat domain containing 1 [KO:K03121]
            2969  GTF2I; general transcription factor IIi [KO:K03121]
            23236  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
            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]
            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]
            10335  IRAG1; inositol 1,4,5-triphosphate receptor associated 1 [KO:K12337]
            5350  PLN; phospholamban [KO:K05852]
            487  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
            489  ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:7.2.2.10]
            488  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
            387  RHOA; ras homolog family member A [KO:K04513]
            6093  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
            9475  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
            4659  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
            5499  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
            5500  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
            5501  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
            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]
            4638  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
            85366  MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
            91807  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
            340156  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
            10398  MYL9; myosin light chain 9 [KO:K12755]
            1259  CNGA1; cyclic nucleotide gated channel subunit alpha 1 [KO:K04948]
            1258  CNGB1; cyclic nucleotide gated channel subunit beta 1 [KO:K04952]
            107  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
            108  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
            109  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
            196883  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
            111  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
            112  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
            113  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
            114  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
            115  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
            5138  PDE2A; phosphodiesterase 2A [KO:K18283] [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]
            8654  PDE5A; phosphodiesterase 5A [KO:K13762] [EC:3.1.4.35]
            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]
            3827  KNG1; kininogen 1 [KO:K03898]
            624  BDKRB2; bradykinin receptor B2 [KO:K03916]
            4985  OPRD1; opioid receptor delta 1 [KO:K04213]
            134  ADORA1; adenosine A1 receptor [KO:K04265]
            140  ADORA3; adenosine A3 receptor [KO:K04268]
            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]
            3630  INS; insulin [KO:K04526]
            3643  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
            3667  IRS1; insulin receptor substrate 1 [KO:K16172]
            8660  IRS2; insulin receptor substrate 2 [KO:K07187]
            8471  IRS4; insulin receptor substrate 4 [KO:K17446]
            5294  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
            23533  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
            146850  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
            207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
            208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
            10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
            4846  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
            153  ADRB1; adrenoceptor beta 1 [KO:K04141]
            154  ADRB2; adrenoceptor beta 2 [KO:K04142]
            155  ADRB3; adrenoceptor beta 3 [KO:K04143]
            5581  PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
            3764  KCNJ8; potassium inwardly rectifying channel subfamily J member 8 [KO:K05001]
            7416  VDAC1; voltage dependent anion channel 1 [KO:K05862]
            7417  VDAC2; voltage dependent anion channel 2 [KO:K15040]
            7419  VDAC3; voltage dependent anion channel 3 [KO:K15041]
            291  SLC25A4; solute carrier family 25 member 4 [KO:K05863]
            292  SLC25A5; solute carrier family 25 member 5 [KO:K05863]
            293  SLC25A6; solute carrier family 25 member 6 [KO:K05863]
            83447  SLC25A31; solute carrier family 25 member 31 [KO:K05863]
            10105  PPIF; peptidylprolyl isomerase F [KO:K09565] [EC:5.2.1.8]
            1385  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
            1386  ATF2; activating transcription factor 2 [KO:K04450]
            468  ATF4; activating transcription factor 4 [KO:K04374]
            10488  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
            90993  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
            64764  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
            84699  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
            148327  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
            9586  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
            1388  ATF6B; activating transcription factor 6 beta [KO:K09049]
            572  BAD; BCL2 associated agonist of cell death [KO:K02158]
            7408  VASP; vasodilator stimulated phosphoprotein [KO:K06274]
            5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
            5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
            5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
            5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
            5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
COMPOUND    C00020  AMP
            C00027  Hydrogen peroxide
            C00076  Calcium cation
            C00144  GMP
            C00212  Adenosine
            C00238  Potassium cation
            C00533  Nitric oxide
            C00575  3',5'-Cyclic AMP
            C00942  3',5'-Cyclic GMP
            C01245  D-myo-Inositol 1,4,5-trisphosphate
REFERENCE   PMID:20716671
  AUTHORS   Francis SH, Busch JL, Corbin JD, Sibley D
  TITLE     cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action.
  JOURNAL   Pharmacol Rev 62:525-63 (2010)
            DOI:10.1124/pr.110.002907
REFERENCE   PMID:16439998
  AUTHORS   Feil R, Kemp-Harper B
  TITLE     cGMP signalling: from bench to bedside. Conference on cGMP generators, effectors and therapeutic implications.
  JOURNAL   EMBO Rep 7:149-53 (2006)
            DOI:10.1038/sj.embor.7400627
REFERENCE   PMID:22785374
  AUTHORS   Takimoto E
  TITLE     Cyclic GMP-dependent signaling in cardiac myocytes.
  JOURNAL   Circ J 76:1819-25 (2012)
            DOI:10.1253/circj.CJ-12-0664
REFERENCE   PMID:16371594
  AUTHORS   Hofmann F, Feil R, Kleppisch T, Schlossmann J
  TITLE     Function of cGMP-dependent protein kinases as revealed by gene deletion.
  JOURNAL   Physiol Rev 86:1-23 (2006)
            DOI:10.1152/physrev.00015.2005
REFERENCE   PMID:21685243
  AUTHORS   Kuebler WM
  TITLE     The Janus-faced regulation of endothelial permeability by cyclic GMP.
  JOURNAL   Am J Physiol Lung Cell Mol Physiol 301:L157-60 (2011)
            DOI:10.1152/ajplung.00192.2011
REFERENCE   PMID:21666108
  AUTHORS   Schlossmann J, Desch M
  TITLE     IRAG and novel PKG targeting in the cardiovascular system.
  JOURNAL   Am J Physiol Heart Circ Physiol 301:H672-82 (2011)
            DOI:10.1152/ajpheart.00198.2011
REFERENCE   PMID:16460276
  AUTHORS   Murthy KS
  TITLE     Signaling for contraction and relaxation in smooth muscle of the gut.
  JOURNAL   Annu Rev Physiol 68:345-74 (2006)
            DOI:10.1146/annurev.physiol.68.040504.094707
REFERENCE   PMID:22965426
  AUTHORS   Sanders KM, Koh SD, Ro S, Ward SM
  TITLE     Regulation of gastrointestinal motility--insights from smooth muscle biology.
  JOURNAL   Nat Rev Gastroenterol Hepatol 9:633-45 (2012)
            DOI:10.1038/nrgastro.2012.168
REFERENCE   PMID:20024580
  AUTHORS   Gao Y
  TITLE     The multiple actions of NO.
  JOURNAL   Pflugers Arch 459:829-39 (2010)
            DOI:10.1007/s00424-009-0773-9
REFERENCE   PMID:9003029
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REL_PATHWAY hsa04010  MAPK signaling pathway
            hsa04020  Calcium signaling pathway
            hsa04151  PI3K-Akt signaling pathway
            hsa04210  Apoptosis
            hsa04270  Vascular smooth muscle contraction
            hsa04744  Phototransduction
KO_PATHWAY  ko04022
///
