Labetalol (T3D3517)

General Function:

Protein heterodimerization activity

Specific Function:

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.

Included Proteins:

P35348 , P35368 , P25100

References

1. Bernstein JS, Ebert TJ, Stowe DF, Schmeling WT, Nelson MA, Woods MP: Partial attenuation of hemodynamic responses to rapid sequence induction and intubation with labetalol. J Clin Anesth. 1989;1(6):444-51. [2696507 ]
2. Nakamura T, Maruyama K, Ohnuki T, Hattori K, Watanabe K, Nagatomo T: Tamsulosin: assessment of affinityof (3)H-P razosin binding to two alpha-1- adrenoceptor subtypes in the canine aorta. Pharmacology. 1999 Nov;59(5):234-8. [10529655 ]
3. Sassard J, Zech PY, Pozet N, Cuisinaud G, Vincent M: [Comparative effects of an alpha 1 and beta 1-2 blocker (labetalol) and a beta-1 blocker (atenolol) in the hypertensive patient]. J Pharmacol. 1983;14 Suppl 2:121-9. [6355664 ]
4. Pedersen ME, Cockcroft JR: The vasodilatory beta-blockers. Curr Hypertens Rep. 2007 Aug;9(4):269-77. [17686376 ]
5. Shiraishi K, Moriya M, Miyake N, Takayanagi I: Alpha 1-adrenoceptor blocking activities of bevantolol hydrochloride(NC-1400) and labetalol in rat isolated thoracic aorta--do they distinguish between subtypes? Gen Pharmacol. 1992 Sep;23(5):843-5. [1358746 ]
6. Rosendorff C: Beta-blocking agents with vasodilator activity. J Hypertens Suppl. 1993 Jun;11(4):S37-40. [8104240 ]
7. van Zwieten PA: An overview of the pharmacodynamic properties and therapeutic potential of combined alpha- and beta-adrenoceptor antagonists. Drugs. 1993 Apr;45(4):509-17. [7684671 ]

General Function:

Receptor signaling protein activity

Specific Function:

Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.

Gene Name:

ADRB1

Uniprot ID:

P08588

Molecular Weight:

51322.1 Da

References

1. Baker JG: The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. Br J Pharmacol. 2005 Feb;144(3):317-22. [15655528 ]
2. Asselin AA, Humber LG, Crosilla D, Oshiro G, Wojdan A, Grimes D, Heaslip RJ, Rimele TJ, Shaw CC: Indole-phenol bioisosterism. Synthesis and antihypertensive activity of a pyrrolo analogue of labetalol. J Med Chem. 1986 Jun;29(6):1009-15. [3012084 ]

General Function:

Protein homodimerization activity

Specific Function:

Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.

Gene Name:

ADRB2

Uniprot ID:

P07550

Molecular Weight:

46458.32 Da

References

1. Wisler JW, DeWire SM, Whalen EJ, Violin JD, Drake MT, Ahn S, Shenoy SK, Lefkowitz RJ: A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. Epub 2007 Oct 9. [17925438 ]

General Function:

Protein homodimerization activity

Specific Function:

Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.

Gene Name:

ADRB3

Uniprot ID:

P13945

Molecular Weight:

43518.615 Da

References

1. Baker JG: The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. Br J Pharmacol. 2005 Feb;144(3):317-22. [15655528 ]

General Function:

Syndecan binding

Specific Function:

Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extacellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis.

Gene Name:

HPSE

Uniprot ID:

Q9Y251

Molecular Weight:

61148.17 Da

References

1. Gozalbes R, Mosulen S, Orti L, Rodriguez-Diaz J, Carbajo RJ, Melnyk P, Pineda-Lucena A: Hit identification of novel heparanase inhibitors by structure- and ligand-based approaches. Bioorg Med Chem. 2013 Apr 1;21(7):1944-51. doi: 10.1016/j.bmc.2013.01.033. Epub 2013 Jan 31. [23415087 ]

General Function:

Protein heterodimerization activity

Specific Function:

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.

Gene Name:

ADRA1A

Uniprot ID:

P35348

Molecular Weight:

51486.005 Da

General Function:

Protein heterodimerization activity

Specific Function:

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.

Gene Name:

ADRA1B

Uniprot ID:

P35368

Molecular Weight:

56835.375 Da