Showing metabocard for Felodipine (HMDB15158)

General function:

Involved in catalytic activity

Specific function:

Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a higher affinity for cGMP than for cAMP.

Gene Name:

PDE1A

Uniprot ID:

P54750

Molecular weight:

61251.38

References

1. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [2933041 ]
2. Sharma RK, Wang JH, Wu Z: Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists. J Neurochem. 1997 Aug;69(2):845-50. [9231746 ]

General function:

Involved in catalytic activity

Specific function:

Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a preference for cGMP as a substrate.

Gene Name:

PDE1B

Uniprot ID:

Q01064

Molecular weight:

61379.235

References

1. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [2933041 ]
2. Sharma RK, Wang JH, Wu Z: Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists. J Neurochem. 1997 Aug;69(2):845-50. [9231746 ]

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.

Gene Name:

CYP3A4

Uniprot ID:

P08684

Molecular weight:

57255.585

References

1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
2. Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. [12433827 ]

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.

Gene Name:

CYP2C9

Uniprot ID:

P11712

Molecular weight:

55627.365

References

1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]

General function:

Involved in monooxygenase activity

Specific function:

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.

Gene Name:

CYP2D6

Uniprot ID:

P10635

Molecular weight:

55768.94

References

1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

Gene Name:

CYP3A5

Uniprot ID:

P20815

Molecular weight:

57108.065

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

Gene Name:

CYP3A7

Uniprot ID:

P24462

Molecular weight:

57525.03

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).

Gene Name:

CYP2C8

Uniprot ID:

P10632

Molecular weight:

55824.275

References

1. Schoch GA, Yano JK, Sansen S, Dansette PM, Stout CD, Johnson EF: Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid. J Biol Chem. 2008 Jun 20;283(25):17227-37. Epub 2008 Apr 15. [18413310 ]
2. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [15601807 ]
3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]

General function:

Involved in calcium ion binding

Specific function:

Calmodulin mediates the control of a large number of enzymes and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CEP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis

Gene Name:

CALM1

Uniprot ID:

P62158

Molecular weight:

16837.5

References

1. Bostrom SL, Westerlund C, Rochester S, Vogel HJ: Binding of a dihydropyridine felodipine-analogue to calmodulin and related calcium-binding proteins. Biochem Pharmacol. 1988 Oct 1;37(19):3723-8. [3178884 ]
2. Johnson JD, Andrews CT, Khabbaza EJ, Mills JS: The interaction of felodipine with calcium-binding proteins. J Cardiovasc Pharmacol. 1987;10 Suppl 1:S53-9. [2442519 ]
3. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [2933041 ]
4. Lamers JM, Verdouw PD, Mas-Oliva J: The effects of felodipine and bepridil on calcium-stimulated calmodulin binding and calcium pumping ATPase of cardiac sarcolemma before and after removal of endogenous calmodulin. Mol Cell Biochem. 1987 Dec;78(2):169-76. [2964559 ]
5. Mills JS, Bailey BL, Johnson JD: Cooperativity among calmodulin's drug binding sites. Biochemistry. 1985 Aug 27;24(18):4897-902. [4074665 ]
6. Walsh MP, Sutherland C, Scott-Woo GC: Effects of felodipine (a dihydropyridine calcium channel blocker) and analogues on calmodulin-dependent enzymes. Biochem Pharmacol. 1988 Apr 15;37(8):1569-80. [2833901 ]

General function:

Involved in ion channel activity

Specific function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA)

Gene Name:

CACNA1D

Uniprot ID:

Q01668

Molecular weight:

245138.8

References

1. Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. Epub 2008 Nov 24. [19029287 ]

General function:

Involved in ion channel activity

Specific function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function

Gene Name:

CACNA1C

Uniprot ID:

Q13936

Molecular weight:

248974.1

References

1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [10525060 ]
3. Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. [17475903 ]

General function:

Involved in sequence-specific DNA binding transcription factor activity

Specific function:

Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels

Gene Name:

NR3C2

Uniprot ID:

P08235

Molecular weight:

107066.6

References

1. Dietz JD, Du S, Bolten CW, Payne MA, Xia C, Blinn JR, Funder JW, Hu X: A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension. 2008 Mar;51(3):742-8. Epub 2008 Feb 4. [18250364 ]

General function:

Involved in metal ion binding

Specific function:

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling

Gene Name:

CACNA2D1

Uniprot ID:

P54289

Molecular weight:

124566.9

References

1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [10525060 ]
3. Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. [17475903 ]

General function:

Involved in calcium channel activity

Specific function:

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosis

Gene Name:

CACNA2D2

Uniprot ID:

Q9NY47

Molecular weight:

129875.2

References

1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [1281221 ]
2. Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. Epub 2008 Oct 30. [18974361 ]

General function:

Involved in ion channel activity

Specific function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1H gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes

Gene Name:

CACNA1H

Uniprot ID:

O95180

Molecular weight:

259160.2

References

1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [1281221 ]
2. Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. Epub 2008 Oct 30. [18974361 ]

General function:

Involved in ion channel activity

Specific function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle

Gene Name:

CACNA1S

Uniprot ID:

Q13698

Molecular weight:

212348.1

References

1. Peterson BZ, Catterall WA: Allosteric interactions required for high-affinity binding of dihydropyridine antagonists to Ca(V)1.1 Channels are modulated by calcium in the pore. Mol Pharmacol. 2006 Aug;70(2):667-75. Epub 2006 May 4. [16675661 ]

General function:

Involved in voltage-gated calcium channel activity

Specific function:

The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting

Gene Name:

CACNB2

Uniprot ID:

Q08289

Molecular weight:

73579.9

References

1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [10525060 ]
3. Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. [17475903 ]

General function:

Involved in calcium ion binding

Specific function:

Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components:Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments

Gene Name:

TNNC1

Uniprot ID:

P63316

Molecular weight:

18402.4

References

1. Bostrom SL, Westerlund C, Rochester S, Vogel HJ: Binding of a dihydropyridine felodipine-analogue to calmodulin and related calcium-binding proteins. Biochem Pharmacol. 1988 Oct 1;37(19):3723-8. [3178884 ]

General function:

Involved in calcium ion binding

Specific function:

Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components:Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments

Gene Name:

TNNC2

Uniprot ID:

P02585

Molecular weight:

18121.9

References

1. Bostrom SL, Westerlund C, Rochester S, Vogel HJ: Binding of a dihydropyridine felodipine-analogue to calmodulin and related calcium-binding proteins. Biochem Pharmacol. 1988 Oct 1;37(19):3723-8. [3178884 ]
2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]