Entry
Name
Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
Description
Cardiac myocytes express at least six subtypes of adrenergic receptor (AR) which include three subtypes of beta-AR (beta-1, beta-2, beta-3) and three subtypes of the alpha-1-AR (alpha-1A, alpha-1B, and alpha-1C). In the human heart the beta-1-AR is the pre- dominate receptor. Acute sympathetic stimulation of cardiac beta-1-ARs induces positive inotropic and chronotropic effects, the most effective mechanism to acutely increase output of the heart, by coupling to Gs, formation of cAMP by adenylyl cyclase (AC), and PKA- dependent phosphorylation of various target proteins (e.g., ryanodine receptor [RyR]; phospholamban [PLB], troponin I [TnI], and the L-type Ca2+ channel [LTCC]). Chronic beta-1-AR stimulation is detrimental and induces cardiomyocyte hypertrophy and apoptosis. beta-2-AR coupled to Gs exerts a proapoptotic action as well as beta-1-AR, while beta-2-AR coupled to Gi exerts an antiapoptotic action.
Class
Organismal Systems; Circulatory system
BRITE hierarchy
Pathway map
hsa04261 Adrenergic signaling in cardiomyocytes
Ortholog table
Network
Element
N01345 EP/NE-ADRB-cAMP signaling pathway
N01347 EP/NE-ADRB-PI3K signaling pathway
Drug
D00235 Atenolol (JP18/USP/INN)
D00255 Carvedilol (JP18/USP/INN)
D00297 Digitoxin (JAN/USP/INN)
D00303 Disopyramide (JP18/USAN/INN)
D00319 Felodipine (JP18/USP/INN)
D00357 Losartan potassium (JP18/USP)
D00358 Lidocaine (JP18/USP/INN)
D00400 Valsartan (JP18/USP/INN)
D00437 Nifedipine (JP18/USP/INN)
D00477 Procainamide hydrochloride (JP18/USP)
D00483 Propranolol hydrochloride (JP18/USP)
D00509 Phentolamine mesylate (USP)
D00511 Phenylephrine hydrochloride (JP18/USP)
D00513 Pindolol (JP18/USP/INN)
D00523 Irbesartan (JP18/USP/INN)
D00597 Acebutolol hydrochloride (JP18/USP)
D00598 Betaxolol hydrochloride (JP18/USP)
D00599 Carteolol hydrochloride (JP18/USP)
D00600 Labetalol hydrochloride (JP18/USP)
D00601 Metoprolol tartrate (JP18/USP)
D00602 Penbutolol sulfate (JP18/USP)
D00603 Timolol maleate (JP18/USP)
D00608 Doxazosin mesylate (USP)
D00609 Prazosin hydrochloride (JP18/USP)
D00615 Amlodipine besylate (USP)
D00616 Diltiazem hydrochloride (JP18/USP)
D00617 Nicardipine hydrochloride (JP18/USAN)
D00618 Nisoldipine (JAN/USAN/INN)
D00626 Candesartan cilexetil (JP18/USP)
D00627 Telmisartan (JP18/USP/INN)
D00629 Nitrendipine (JP18/USAN/INN)
D00632 Dobutamine hydrochloride (JP18/USP)
D00634 Bisoprolol fumarate (JP18/USP)
D00635 Metoprolol succinate (USP)
D00636 Amiodarone hydrochloride (JP18/USP)
D00637 Disopyramide phosphate (JAN/USP)
D00638 Flecainide acetate (JP18/USP)
D00639 Mexiletine hydrochloride (JP18/USP)
D00640 Propafenone hydrochloride (JP18/USP)
D00642 Quinidine gluconate (USP)
D00643 Quinidine polygalacturonate
D00644 Esmolol hydrochloride (JAN/USP)
D00645 Bretylium tosylate (USP)
D00996 Epinephrine hydrochloride (JAN)
D00997 Tolazoline hydrochloride (JAN/USP)
D01019 Metaraminol bitartrate (JAN/USP)
D01020 Methoxamine hydrochloride (JAN)
D01026 Sotalol hydrochloride (JAN/USP)
D01104 Barnidipine hydrochloride (JAN)
D01145 Azelnidipine (JP18/INN)
D01171 Monatepil maleate (JAN/USAN)
D01182 Alprenolol hydrochloride (JP18/USAN)
D01204 Olmesartan medoxomil (JP18/USP)
D01240 Deslanoside (JP18/USP/INN)
D01277 Droxidopa (JP18/USAN/INN)
D01326 Aprindine hydrochloride (JP18/USAN)
D01369 Bevantolol hydrochloride (JAN/USAN)
D01379 Proscillaridin (JAN/USAN/INN)
D01386 Ephedrine hydrochloride (JP18/USP)
D01390 Isoproterenol hydrochloride (USP)
D01444 Bunitrolol hydrochloride (JAN)
D01454 Bupranolol hydrochloride (JP18)
D01455 Cifenline succinate (USAN)
D01469 Amosulalol hydrochloride (JP18)
D01492 Bucumolol hydrochloride (JP18)
D01504 Bufetolol hydrochloride (JP18)
D01553 Manidipine hydrochloride (JP18)
D01573 Etilefrine hydrochloride (JP18)
D01604 Efonidipine hydrochloride ethanolate (JAN)
D01697 Colforsin daropate hydrochloride (JAN)
D01741 Celiprolol hydrochloride (JAN/USAN)
D01748 Isoxsuprine hydrochloride (JP18/USP)
D01785 Pirmenol hydrochloride hydrate (JAN)
D01794 Bopindolol malonate (JAN)
D01795 Tilisolol hydrochloride (JAN)
D01806 Oxprenolol hydrochloride (JP18/USP)
D01830 Arotinolol hydrochloride (JP18)
D01847 Landiolol hydrochloride (JAN/USAN)
D01849 Lercanidipine hydrochloride (JAN/USAN)
D01906 Dilevalol hydrochloride (JAN/USAN)
D01908 Nilvadipine (JP18/USAN/INN)
D01933 Vatanidipine hydrochloride (JAN)
D01958 Indenolol hydrochloride (JP18)
D01969 Gallopamil hydrochloride (JAN)
D02045 Benidipine hydrochloride (JP18)
D02066 Isoproterenol sulfate (USP)
D02082 Eprosartan mesylate (USAN)
D02086 Lidocaine hydrochloride (JAN/USP)
D02087 Moricizine hydrochloride (USP)
D02088 Tocainide hydrochloride (USP)
D02109 dl-Methylephedrine hydrochloride (JP18)
D02149 Epinephrine bitartrate (JAN/USP)
D02150 l-Isoprenaline hydrochloride (JP18)
D02239 Sparteine sulfate (JAN/USAN)
D02272 Quinidine sulfate (USP)
D02342 Bisoprolol (JAN/USAN/INN)
D02765 Adaprolol maleate (USAN)
D02834 Alprenoxime hydrochloride (USAN)
D02901 Amidephrine mesylate (USAN)
D02914 Amlodipine maleate (USAN)
D02939 Angiotensin amide (USAN)
D02976 Arbutamine hydrochloride (USAN)
D03170 Bucindolol hydrochloride (USAN)
D03406 Cariporide mesylate (USAN)
D03415 Carvedilol phosphate (USAN)
D03449 Cetamolol hydrochloride (USAN)
D03490 Cicloprolol hydrochloride (USAN)
D03536 Clentiazem maleate (JAN/USAN)
D03729 Dexpropranolol hydrochloride (USAN)
D03759 Diacetolol hydrochloride (USAN)
D03830 Diltiazem malate (USAN)
D03880 Dobutamine lactobionate (USAN)
D03881 Dobutamine tartrate (USAN)
D03892 Dopexamine hydrochloride (USAN)
D03914 Dronedarone hydrochloride (USP)
D03991 Encainide hydrochloride (USAN)
D04018 Ephedrine sulfate (USP)
D04120 Exaprolol hydrochloride (USAN)
D04190 Flestolol sulfate (USAN)
D04510 Imciromab pentetate (USAN)
D04521 Indecainide hydrochloride (USAN)
D04532 Indoramin hydrochloride (USAN)
D04708 Levdobutamine lactobionate (USAN)
D04710 Levobetaxolol hydrochloride (USAN)
D04774 Lorajmine hydrochloride (USAN)
D04889 Medroxalol hydrochloride (USAN)
D05011 Metoprolol fumarate (USP)
D05024 Mibefradil dihydrochloride (USAN)
D05206 Norepinephrine bitartrate (USP)
D05345 Pamatolol sulfate (USAN)
D05442 Perhexiline maleate (USAN)
D05801 Saprisartan potassium (USAN)
D06014 Tazolol hydrochloride (USAN)
D06162 Tiprenolol hydrochloride (USAN)
D06203 Transcainide (USAN/INN)
D06234 Trimazosin hydrochloride (USAN)
D06329 Xamoterol fumarate (USAN)
D06517 Pirmenol hydrochloride (USAN)
D06622 Nebivolol hydrochloride (USAN)
D06665 Vernakalant hydrochloride (USAN)
D07943 Fendiline hydrochloride
D08067 Azilsartan medoxomil (USAN)
D08127 Lidocaine hydrochloride monohydrate
D08284 Norepinephrine hydrochoride
D08459 Quinidine phenylethylbarbiturate
D08572 Tertatolol hydrochloride
D08865 Azilsartan kamedoxomil (USAN)
D08941 Levamlodipine malate (USAN)
D08966 Phenylephrine bitartrate (USP)
D09789 Kirenidipine hydrochloride (JAN)
D09794 Norepinephrine hydrochloride (JAN)
D09833 Levosemotiadil fumarate (JAN)
D09843 Beradilol monoethyl maleate (JAN)
D11142 Angiotensin II acetate (USAN)
D11585 Terazosin hydrochloride anhydrous
D11723 Levamlodipine maleate (USAN)
D12265 Mavacamten (JAN/USAN/INN)
D12840 Zilebesiran sodium (JAN/USAN)
D12934 Dibutepinephrine (USAN/INN)
D12935 Dibutepinephrine hydrochloride (USAN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
102723475 KCNE1B; potassium voltage-gated channel subfamily E regulatory subunit 1B [KO:K04894 ]
10368 CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868 ]
10369 CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867 ]
10411 RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO:K08014 ]
10488 CREB3; cAMP responsive element binding protein 3 [KO:K09048 ]
11069 RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO:K04351 ]
11149 POPDC1; popeye domain cAMP effector 1 [KO:K21108 ]
1385 CREB1; cAMP responsive element binding protein 1 [KO:K05870 ]
1386 ATF2; activating transcription factor 2 [KO:K04450 ]
1388 ATF6B; activating transcription factor 6 beta [KO:K09049 ]
1390 CREM; cAMP responsive element modulator [KO:K09052 ]
146 ADRA1D; adrenoceptor alpha 1D [KO:K04137 ]
146850 PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290 ]
147 ADRA1B; adrenoceptor alpha 1B [KO:K04136 ]
148 ADRA1A; adrenoceptor alpha 1A [KO:K04135 ]
148327 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
185 AGTR1; angiotensin II receptor type 1 [KO:K04166 ]
186 AGTR2; angiotensin II receptor type 2 [KO:K04167 ]
23439 ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540 ]
23533 PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290 ]
27091 CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870 ]
27092 CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869 ]
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 ]
28227 PPP2R3B; protein phosphatase 2 regulatory subunit B''beta [KO:K11583 ]
3753 KCNE1; potassium voltage-gated channel subfamily E regulatory subunit 1 [KO:K04894 ]
3776 KCNK2; potassium two pore domain channel subfamily K member 2 [KO:K04913 ]
3784 KCNQ1; potassium voltage-gated channel subfamily Q member 1 [KO:K04926 ]
468 ATF4; activating transcription factor 4 [KO:K04374 ]
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 ]
487 ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853 ] [EC:7.2.2.10 ]
488 ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853 ] [EC:7.2.2.10 ]
489 ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853 ] [EC:7.2.2.10 ]
5294 PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289 ] [EC:2.7.1.153 ]
55012 PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583 ]
5502 PPP1R1A; protein phosphatase 1 regulatory inhibitor subunit 1A [KO:K08050 ]
5518 PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456 ]
5519 PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456 ]
5520 PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354 ]
5521 PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354 ]
5522 PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354 ]
5523 PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583 ]
5525 PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584 ]
5526 PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584 ]
5527 PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584 ]
5528 PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584 ]
5529 PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584 ]
55799 CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860 ]
55844 PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354 ]
59283 CACNG8; calcium voltage-gated channel auxiliary subunit gamma 8 [KO:K04873 ]
59284 CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872 ]
59285 CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871 ]
596 BCL2; BCL2 apoptosis regulator [KO:K02161 ]
6324 SCN1B; sodium voltage-gated channel beta subunit 1 [KO:K04845 ]
6330 SCN4B; sodium voltage-gated channel beta subunit 4 [KO:K04848 ]
6331 SCN5A; sodium voltage-gated channel alpha subunit 5 [KO:K04838 ]
6332 SCN7A; sodium voltage-gated channel alpha subunit 7 [KO:K04839 ]
64091 POPDC2; popeye domain cAMP effector 2 [KO:K26206 ]
64208 POPDC3; popeye domain cAMP effector 3 [KO:K26207 ]
64764 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
6543 SLC8A2; solute carrier family 8 member A2 [KO:K05849 ]
6546 SLC8A1; solute carrier family 8 member A1 [KO:K05849 ]
6547 SLC8A3; solute carrier family 8 member A3 [KO:K05849 ]
6548 SLC9A1; solute carrier family 9 member A1 [KO:K05742 ]
70 ACTC1; actin alpha cardiac muscle 1 [KO:K12314 ]
7134 TNNC1; troponin C1, slow skeletal and cardiac type [KO:K05865 ]
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 ]
781 CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858 ]
782 CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862 ]
783 CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863 ]
784 CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864 ]
785 CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865 ]
786 CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866 ]
815 CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515 ] [EC:2.7.11.17 ]
816 CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515 ] [EC:2.7.11.17 ]
817 CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515 ] [EC:2.7.11.17 ]
818 CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515 ] [EC:2.7.11.17 ]
84699 CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048 ]
90993 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
9254 CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859 ]
93589 CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861 ]
9586 CREB5; cAMP responsive element binding protein 5 [KO:K09047 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference
Authors
Grimm M, Brown JH
Title
Beta-adrenergic receptor signaling in the heart: role of CaMKII.
Journal
Reference
Authors
Yang JH, Saucerman JJ
Title
Computational models reduce complexity and accelerate insight into cardiac signaling networks.
Journal
Reference
Authors
Schaub MC, Hefti MA, Zaugg M
Title
Integration of calcium with the signaling network in cardiac myocytes.
Journal
Reference
Authors
Taggart P, Boyett MR, Logantha S, Lambiase PD
Title
Anger, emotion, and arrhythmias: from brain to heart.
Journal
Reference
Authors
Bers DM
Title
Calcium cycling and signaling in cardiac myocytes.
Journal
Reference
Authors
Soltis AR, Saucerman JJ
Title
Synergy between CaMKII substrates and beta-adrenergic signaling in regulation of cardiac myocyte Ca(2+) handling.
Journal
Reference
Authors
Wallukat G
Title
The beta-adrenergic receptors.
Journal
Reference
Authors
Xiao RP
Title
Beta-adrenergic signaling in the heart: dual coupling of the beta2-adrenergic receptor to G(s) and G(i) proteins.
Journal
Reference
Authors
Xiao RP, Cheng H, Zhou YY, Kuschel M, Lakatta EG
Title
Recent advances in cardiac beta(2)-adrenergic signal transduction.
Journal
Reference
Authors
Zheng M, Zhu W, Han Q, Xiao RP
Title
Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling.
Journal
Reference
Authors
Kuzumoto M, Takeuchi A, Nakai H, Oka C, Noma A, Matsuoka S
Title
Simulation analysis of intracellular Na+ and Cl- homeostasis during beta 1-adrenergic stimulation of cardiac myocyte.
Journal
Reference
Authors
Bers DM
Title
Cardiac excitation-contraction coupling.
Journal
Reference
Authors
Ho D, Yan L, Iwatsubo K, Vatner DE, Vatner SF
Title
Modulation of beta-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5.
Journal
Reference
Authors
Saucerman JJ, McCulloch AD
Title
Mechanistic systems models of cell signaling networks: a case study of myocyte adrenergic regulation.
Journal
Reference
Authors
Yano M, Ikeda Y, Matsuzaki M
Title
Altered intracellular Ca2+ handling in heart failure.
Journal
Reference
Authors
Wehrens XH, Marks AR
Title
Novel therapeutic approaches for heart failure by normalizing calcium cycling.
Journal
Reference
Authors
Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J
Title
The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications.
Journal
Reference
Authors
Barry SP, Davidson SM, Townsend PA
Title
Molecular regulation of cardiac hypertrophy.
Journal
Related pathway
KO pathway