Nitric Oxide Signaling in the Cardiovascular System
Nitric oxide (NO) is produced in the vascular system by endothelial nitric oxide synthase (eNOS), a Ca+2/calmodulin (CaM)-dependent enzyme. NO production is promoted by diverse agonists that transiently increase intracellular Ca+2 concentration and activate eNOS. For example, interaction of eNOS with caveolin, the structural scaffolding protein of caveolae reduces eNOS activity. The calveolin-eNOS complex undergoes cycles of association and dissociation modulated by Ca+2 concentrations. Other regulators of eNOS action include HSP90 and Akt which synergistically increase eNOS activity along with formation of a ternary complex comprised of HSP90, Akt, and CaM-bound eNOS...
Pathway Summary
Nitric oxide (NO) is produced in the vascular system by endothelial nitric oxide synthase (eNOS), a Ca+2/calmodulin (CaM)-dependent enzyme. NO production is promoted by diverse agonists that transiently increase intracellular Ca+2 concentration and activate eNOS. For example, interaction of eNOS with caveolin, the structural scaffolding protein of caveolae reduces eNOS activity. The calveolin-eNOS complex undergoes cycles of association and dissociation modulated by Ca+2 concentrations. Other regulators of eNOS action include HSP90 and Akt which synergistically increase eNOS activity along with formation of a ternary complex comprised of HSP90, Akt, and CaM-bound eNOS.In the heart, excitation-contraction (EC) coupling is driven by an ion-channel-mediated calcium cycle that produces myofilament contraction and relaxation. NO in the heart is able to regulate the activaty of ion channels like the L-type Ca(+2). These effects are mediated by cGMP, through the activity of three main proteins: the cGMP-dependent protein kinase (PKG), the cGMP-stimulated phosphodiesterase (PDE2) and the cGMP-inhibited PDE (PDE3). There is also evidence that NO may modulate the function of the ryanodine receptor Ca(2+) release channel (RyR2) on the cardiac sarcoplasmic reticulum.
Nitric Oxide Signaling in the Cardiovascular System Genes list
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ADRB1adrenoceptor beta 1 ADRB3adrenoceptor beta 3 AKT1AKT serine/threonine kinase 1 AKT2AKT serine/threonine kinase 2 AKT3AKT serine/threonine kinase 3 ARG2arginase 2 ATP2A1ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 ATP2A2ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 ATP2A3ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 BDKRB2bradykinin receptor B2 CACNA1Acalcium voltage-gated channel subunit alpha1 A CACNA1Bcalcium voltage-gated channel subunit alpha1 B CACNA1Ccalcium voltage-gated channel subunit alpha1 C CACNA1Dcalcium voltage-gated channel subunit alpha1 D CACNA1Ecalcium voltage-gated channel subunit alpha1 E CACNA1Fcalcium voltage-gated channel subunit alpha1 F CACNA1Scalcium voltage-gated channel subunit alpha1 S CACNA2D1calcium voltage-gated channel auxiliary subunit alpha2delta 1 CACNA2D2calcium voltage-gated channel auxiliary subunit alpha2delta 2 CACNA2D3calcium voltage-gated channel auxiliary subunit alpha2delta 3 CACNA2D4calcium voltage-gated channel auxiliary subunit alpha2delta 4 CACNB1calcium voltage-gated channel auxiliary subunit beta 1 CACNB2calcium voltage-gated channel auxiliary subunit beta 2 CACNB3calcium voltage-gated channel auxiliary subunit beta 3 CACNB4calcium voltage-gated channel auxiliary subunit beta 4 CACNG1calcium voltage-gated channel auxiliary subunit gamma 1 CACNG2calcium voltage-gated channel auxiliary subunit gamma 2 CACNG3calcium voltage-gated channel auxiliary subunit gamma 3 CACNG4calcium voltage-gated channel auxiliary subunit gamma 4 CACNG5calcium voltage-gated channel auxiliary subunit gamma 5 CACNG6calcium voltage-gated channel auxiliary subunit gamma 6 CACNG7calcium voltage-gated channel auxiliary subunit gamma 7 CACNG8calcium voltage-gated channel auxiliary subunit gamma 8 CALML5calmodulin like 5 CAMPcathelicidin antimicrobial peptide CAV1caveolin 1 CHRM1cholinergic receptor muscarinic 1 FLT1fms related receptor tyrosine kinase 1 FLT4fms related receptor tyrosine kinase 4 GUCY1A1guanylate cyclase 1 soluble subunit alpha 1 GUCY1A2guanylate cyclase 1 soluble subunit alpha 2 GUCY1B1guanylate cyclase 1 soluble subunit beta 1 GUCY1B2guanylate cyclase 1 soluble subunit beta 2 (pseudogene) GUCY2Cguanylate cyclase 2C GUCY2Dguanylate cyclase 2D, retinal GUCY2Fguanylate cyclase 2F, retinal HSP90AA1heat shock protein 90 alpha family class A member 1 HSP90AB1heat shock protein 90 alpha family class B member 1 HSP90B1heat shock protein 90 beta family member 1 ITPR1inositol 1,4,5-trisphosphate receptor type 1 ITPR2inositol 1,4,5-trisphosphate receptor type 2 ITPR3inositol 1,4,5-trisphosphate receptor type 3 KDRkinase insert domain receptor MAP2K1mitogen-activated protein kinase kinase 1 MAP2K2mitogen-activated protein kinase kinase 2 MAPK1mitogen-activated protein kinase 1 MAPK14mitogen-activated protein kinase 14 MAPK3mitogen-activated protein kinase 3 NOS3nitric oxide synthase 3 NPR1natriuretic peptide receptor 1 NPR2natriuretic peptide receptor 2 PDE1Aphosphodiesterase 1A PDE1Bphosphodiesterase 1B PDE1Cphosphodiesterase 1C PDE2Aphosphodiesterase 2A PDE3Bphosphodiesterase 3B PDE5Aphosphodiesterase 5A PDGFCplatelet derived growth factor C PGFplacental growth factor PIK3C2Aphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PIK3C2Bphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta PIK3C2Gphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma PIK3C3phosphatidylinositol 3-kinase catalytic subunit type 3 PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3R1phosphoinositide-3-kinase regulatory subunit 1 PIK3R2phosphoinositide-3-kinase regulatory subunit 2 PIK3R3phosphoinositide-3-kinase regulatory subunit 3 PIK3R4phosphoinositide-3-kinase regulatory subunit 4 PIK3R5phosphoinositide-3-kinase regulatory subunit 5 PIK3R6phosphoinositide-3-kinase regulatory subunit 6 PLNphospholamban PRKAA1protein kinase AMP-activated catalytic subunit alpha 1 PRKACAprotein kinase cAMP-activated catalytic subunit alpha PRKACBprotein kinase cAMP-activated catalytic subunit beta PRKACGprotein kinase cAMP-activated catalytic subunit gamma PRKAG1protein kinase AMP-activated non-catalytic subunit gamma 1 PRKAG2protein kinase AMP-activated non-catalytic subunit gamma 2 PRKAR1Aprotein kinase cAMP-dependent type I regulatory subunit alpha PRKAR1Bprotein kinase cAMP-dependent type I regulatory subunit beta PRKAR2Aprotein kinase cAMP-dependent type II regulatory subunit alpha PRKAR2Bprotein kinase cAMP-dependent type II regulatory subunit beta PRKCAprotein kinase C alpha PRKCBprotein kinase C beta PRKCDprotein kinase C delta PRKCEprotein kinase C epsilon PRKCGprotein kinase C gamma PRKCHprotein kinase C eta PRKCIprotein kinase C iota PRKCQprotein kinase C theta PRKCZprotein kinase C zeta PRKD1protein kinase D1 PRKD3protein kinase D3 PRKG1protein kinase cGMP-dependent 1 PRKG2protein kinase cGMP-dependent 2 PROK1prokineticin 1 RYR2ryanodine receptor 2 SLC7A1solute carrier family 7 member 1 VEGFAvascular endothelial growth factor A VEGFBvascular endothelial growth factor B VEGFCvascular endothelial growth factor C VEGFDvascular endothelial growth factor D
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