Alpha-1B adrenergic receptor explained

The alpha-1B adrenergic receptor (α_1B-adrenoreceptor), also known as ADRA1B, is an alpha-1 adrenergic receptor, and also denotes the human gene encoding it. The crystal structure of the α_1B-adrenergic receptor has been determined in complex with the inverse agonist (+)-cyclazosin.^[1]

Receptor

There are 3 alpha-1 adrenergic receptor subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins and different subtypes show different patterns of activation. They activate mitogenic responses and regulate growth and proliferation of many cells.

Gene

This gene encodes alpha-1B-adrenergic receptor, which induces neoplastic transformation when transfected into NIH 3T3 fibroblasts and other cell lines. Thus, this normal cellular gene is identified as a protooncogene. This gene comprises 2 exons and a single large intron of at least 20 kb that interrupts the coding region.^[2]

Ligands

Antagonists

• L-765,314^[3]
• Risperidone
• Brexpiprazole

Interactions

Alpha-1B adrenergic receptor has been shown to interact with AP2M1.^[4] A role in regulation of dopaminergic neurotransmission has also been suggested.^{[5] [6]}

See also

• Adrenergic receptor

Further reading

• Ramarao CS, Denker JM, Perez DM . Genomic organization and expression of the human alpha 1B-adrenergic receptor. . J. Biol. Chem. . 267 . 30 . 21936–45 . 1992 . 10.1016/S0021-9258(19)36703-1 . 1328250 . etal. free .
• Allen LF, Lefkowitz RJ, Caron MG, Cotecchia S . G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the alpha 1B-adrenergic receptor enhances mitogenesis and tumorigenicity . Proc. Natl. Acad. Sci. U.S.A. . 88 . 24 . 11354–8 . 1992 . 1662393 . 10.1073/pnas.88.24.11354 . 53133 . free .
• Lomasney JW, Cotecchia S, Lorenz W . Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor. The gene for which is located on human chromosome 5 . J. Biol. Chem. . 266 . 10 . 6365–9 . 1991 . 10.1016/S0021-9258(18)38126-2 . 1706716 . etal. free .
• Yang-Feng TL, Xue FY, Zhong WW . Chromosomal organization of adrenergic receptor genes . Proc. Natl. Acad. Sci. U.S.A. . 87 . 4 . 1516–20 . 1990 . 2154750 . 10.1073/pnas.87.4.1516 . 53506 . 1990PNAS...87.1516Y . etal. free .
• Schwinn DA, Johnston GI, Page SO . Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues . J. Pharmacol. Exp. Ther. . 272 . 1 . 134–42 . 1995 . 7815325 . etal.
• Weinberg DH, Trivedi P, Tan CP . Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c . Biochem. Biophys. Res. Commun. . 201 . 3 . 1296–304 . 1994 . 8024574 . 10.1006/bbrc.1994.1845 . etal.
• Forray C, Bard JA, Wetzel JM . The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype . Mol. Pharmacol. . 45 . 4 . 703–8 . 1994 . 8183249 . etal.
• Diviani D, Lattion AL, Larbi N . Effect of different G protein-coupled receptor kinases on phosphorylation and desensitization of the alpha1B-adrenergic receptor . J. Biol. Chem. . 271 . 9 . 5049–58 . 1996 . 8617782 . 10.1074/jbc.271.9.5049 . etal. free .
• Diviani D, Lattion AL, Cotecchia S . Characterization of the phosphorylation sites involved in G protein-coupled receptor kinase- and protein kinase C-mediated desensitization of the alpha1B-adrenergic receptor . J. Biol. Chem. . 272 . 45 . 28712–9 . 1997 . 9353340 . 10.1074/jbc.272.45.28712 . free .
• Qian A, Wang W, Sanborn BM . Evidence for the involvement of several intracellular domains in the coupling of oxytocin receptor to G alpha(q/11) . Cell. Signal. . 10 . 2 . 101–5 . 1998 . 9481484 . 10.1016/S0898-6568(97)00097-1 .
• Sasaguri T, Teruya H, Ishida A . Linkage between alpha(1) adrenergic receptor and the Jak/STAT signaling pathway in vascular smooth muscle cells . Biochem. Biophys. Res. Commun. . 268 . 1 . 25–30 . 2000 . 10652206 . 10.1006/bbrc.1999.2066 . etal.
• Minneman KP, Lee D, Zhong H . Transcriptional responses to growth factor and G protein-coupled receptors in PC12 cells: comparison of alpha(1)-adrenergic receptor subtypes . J. Neurochem. . 74 . 6 . 2392–400 . 2000 . 10820200 . 10.1046/j.1471-4159.2000.0742392.x . 16002509 . etal. free .
• Shibata K, Katsuma S, Koshimizu T . alpha 1-Adrenergic receptor subtypes differentially control the cell cycle of transfected CHO cells through a cAMP-dependent mechanism involving p27Kip1 . J. Biol. Chem. . 278 . 1 . 672–8 . 2003 . 12409310 . 10.1074/jbc.M201375200 . etal. free .
• Diviani D, Lattion AL, Abuin L . The adaptor complex 2 directly interacts with the alpha 1b-adrenergic receptor and plays a role in receptor endocytosis . J. Biol. Chem. . 278 . 21 . 19331–40 . 2003 . 12644451 . 10.1074/jbc.M302110200 . etal. free .
• Gonzalez-Cabrera PJ, Gaivin RJ, Yun J . Genetic profiling of alpha 1-adrenergic receptor subtypes by oligonucleotide microarrays: coupling to interleukin-6 secretion but differences in STAT3 phosphorylation and gp-130 . Mol. Pharmacol. . 63 . 5 . 1104–16 . 2003 . 12695539 . 10.1124/mol.63.5.1104 . 10868191 . etal.
• Pupo AS, Minneman KP . Specific interactions between gC1qR and alpha1-adrenoceptor subtypes . J. Recept. Signal Transduct. Res. . 23 . 2–3 . 185–95 . 2004 . 14626446 . 10.1081/RRS-120025200 . 29600903 .
• Hague C, Uberti MA, Chen Z . Cell surface expression of alpha1D-adrenergic receptors is controlled by heterodimerization with alpha1B-adrenergic receptors . J. Biol. Chem. . 279 . 15 . 15541–9 . 2004 . 14736874 . 10.1074/jbc.M314014200 . etal. free .
• Kang SK, Yi KS, Kwon NS . Alpha1B-adrenoceptor signaling and cell motility: GTPase function of Gh/transglutaminase 2 inhibits cell migration through interaction with cytoplasmic tail of integrin alpha subunits . J. Biol. Chem. . 279 . 35 . 36593–600 . 2004 . 15220331 . 10.1074/jbc.M402084200 . etal. free .
• Gonzalez-Cabrera PJ, Shi T, Yun J . Differential regulation of the cell cycle by alpha1-adrenergic receptor subtypes . Endocrinology . 145 . 11 . 5157–67 . 2004 . 15297446 . 10.1210/en.2004-0728 . etal. free .
• Zhang T, Xu Q, Chen FR . Yeast two-hybrid screening for proteins that interact with alpha1-adrenergic receptors . Acta Pharmacol. Sin. . 25 . 11 . 1471–8 . 2005 . 15525470 . etal.

Notes and References

1. Deluigi M, Morstein L, Schuster M, Klenk C, Merklinger L, Cridge RR, de Zhang LA, Klipp A, Vacca S, Vaid TM, Mittl PR, Egloff P, Eberle SA, Zerbe O, Chalmers DK, Scott DJ, Plückthun A . Crystal structure of the α1B-adrenergic receptor reveals molecular determinants of selective ligand recognition . Nature Communications . 13 . 1 . 382 . January 2022 . 10.1038/s41467-021-27911-3 . 35046410 . 8770593 . 2022NatCo..13..382D .
2. Web site: Entrez Gene: ADRA1B adrenergic, alpha-1B-, receptor.
3. Mizusawa H, Hedlund P, Sjunnesson J, Brioni JD, Sullivan JP, Andersson KE . Enhancement of apomorphine-induced penile erection in the rat by a selective alpha(1D)-adrenoceptor antagonist . Br. J. Pharmacol. . 136 . 5 . 701–8 . 2002 . 12086979 . 1573401 . 10.1038/sj.bjp.0704773 .
4. May 2003 . Diviani D, Lattion AL, Abuin L, Staub O, Cotecchia S . The adaptor complex 2 directly interacts with the alpha 1b-adrenergic receptor and plays a role in receptor endocytosis . J. Biol. Chem. . 278 . 21 . 19331–40 . 12644451 . 10.1074/jbc.M302110200. free .
5. Drouin C, Darracq L, Trovero F, Blanc G, Glowinski J, Cotecchia S, Tassin JP . April 2002 . Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates . J. Neurosci. . 22 . 7 . 2873–84 . 11923452 . 10.1523/jneurosci.22-07-02873.2002. 6758308 . free .
6. Auclair A, Drouin C, Cotecchia S, Glowinski J, Tassin JP . December 2004 . 5-HT2A and alpha1b-adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants . Eur. J. Neurosci. . 20 . 11 . 3073–84 . 15579162 . 10.1111/j.1460-9568.2004.03805.x. 25138763 .