Alpha-1D adrenergic receptor explained

The alpha-1D adrenergic receptor (α_1D adrenoreceptor), also known as ADRA1D, is an alpha-1 adrenergic receptor, and also denotes the human gene encoding it.

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-1D-adrenergic receptor. Similar to alpha-1B-adrenergic receptor gene, this gene comprises 2 exons and a single intron that interrupts the coding region.^[1]

Ligands

Many α₁ receptor ligands are non-selective for receptor subtypes.

Antagonists

• A-315456^[2]
• BMY 7378 (also α_2C antagonist)^[3]
• Domesticine^[4]
• Cyclazosin (slight α_1C selectivity)^[5]
• Tamsulosin (roughly equal affinity for α_1A)

See also

• Adrenergic receptor

Further reading

• Schwinn DA, Lomasney JW . Pharmacologic characterization of cloned alpha 1-adrenoceptor subtypes: selective antagonists suggest the existence of a fourth subtype . European Journal of Pharmacology . 227 . 4 . 433–436 . December 1992 . 1359975 . 10.1016/0922-4106(92)90162-O .
• Bruno JF, Whittaker J, Song JF, Berelowitz M . Molecular cloning and sequencing of a cDNA encoding a human alpha 1A adrenergic receptor . Biochemical and Biophysical Research Communications . 179 . 3 . 1485–1490 . September 1991 . 1656955 . 10.1016/0006-291X(91)91740-4 .
• Esbenshade TA, Hirasawa A, Tsujimoto G, Tanaka T, Yano J, Minneman KP, Murphy TJ . Cloning of the human alpha 1d-adrenergic receptor and inducible expression of three human subtypes in SK-N-MC cells . Molecular Pharmacology . 47 . 5 . 977–985 . May 1995 . 7746284 .
• Schwinn DA, Johnston GI, Page SO, Mosley MJ, Wilson KH, Worman NP, Campbell S, Fidock MD, Furness LM, Parry-Smith DJ . Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues . The Journal of Pharmacology and Experimental Therapeutics . 272 . 1 . 134–142 . January 1995 . 7815325 .
• Weinberg DH, Trivedi P, Tan CP, Mitra S, Perkins-Barrow A, Borkowski D, Strader CD, Bayne M . Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c . Biochemical and Biophysical Research Communications . 201 . 3 . 1296–1304 . June 1994 . 8024574 . 10.1006/bbrc.1994.1845 .
• Loftus SK, Shiang R, Warrington JA, Bengtsson U, McPherson JD, Wasmuth JJ . Genes encoding adrenergic receptors are not clustered on the long arm of human chromosome 5 . Cytogenetics and Cell Genetics . 67 . 2 . 69–74 . 1994 . 8039425 . 10.1159/000133802 .
• Yang-Feng TL, Han H, Lomasney JW, Caron MG . Localization of the cDNA for an alpha 1-adrenergic receptor subtype (ADRA1D) to chromosome band 20p13 . Cytogenetics and Cell Genetics . 66 . 3 . 170–171 . 1994 . 8125015 . 10.1159/000133693 .
• Forray C, Bard JA, Wetzel JM, Chiu G, Shapiro E, Tang R, Lepor H, Hartig PR, Weinshank RL, Branchek TA . The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype . Molecular Pharmacology . 45 . 4 . 703–708 . April 1994 . 8183249 .
• Minneman KP, Lee D, Zhong H, Berts A, Abbott KL, Murphy TJ . Transcriptional responses to growth factor and G protein-coupled receptors in PC12 cells: comparison of alpha(1)-adrenergic receptor subtypes . Journal of Neurochemistry . 74 . 6 . 2392–2400 . June 2000 . 10820200 . 10.1046/j.1471-4159.2000.0742392.x . 16002509 . free .
• Keffel S, Alexandrov A, Goepel M, Michel MC . alpha(1)-adrenoceptor subtypes differentially couple to growth promotion and inhibition in Chinese hamster ovary cells . Biochemical and Biophysical Research Communications . 272 . 3 . 906–911 . June 2000 . 10860850 . 10.1006/bbrc.2000.2850 .
• Kyprianou N, Benning CM . Suppression of human prostate cancer cell growth by alpha1-adrenoceptor antagonists doxazosin and terazosin via induction of apoptosis . Cancer Research . 60 . 16 . 4550–4555 . August 2000 . 10969806 .
• Shibata K, Katsuma S, Koshimizu T, Shinoura H, Hirasawa A, Tanoue A, Tsujimoto G . alpha 1-Adrenergic receptor subtypes differentially control the cell cycle of transfected CHO cells through a cAMP-dependent mechanism involving p27Kip1 . The Journal of Biological Chemistry . 278 . 1 . 672–678 . January 2003 . 12409310 . 10.1074/jbc.M201375200 . free .
• Pupo AS, Minneman KP . Specific interactions between gC1qR and alpha1-adrenoceptor subtypes . Journal of Receptor and Signal Transduction Research . 23 . 2-3 . 185–195 . 2004 . 14626446 . 10.1081/RRS-120025200 . 29600903 .
• Hague C, Uberti MA, Chen Z, Hall RA, Minneman KP . Cell surface expression of alpha1D-adrenergic receptors is controlled by heterodimerization with alpha1B-adrenergic receptors . The Journal of Biological Chemistry . 279 . 15 . 15541–15549 . April 2004 . 14736874 . 10.1074/jbc.M314014200 . free .
• Gonzalez-Cabrera PJ, Shi T, Yun J, McCune DF, Rorabaugh BR, Perez DM . Differential regulation of the cell cycle by alpha1-adrenergic receptor subtypes . Endocrinology . 145 . 11 . 5157–5167 . November 2004 . 15297446 . 10.1210/en.2004-0728 . free .
• Zhang T, Xu Q, Chen FR, Han QD, Zhang YY . Yeast two-hybrid screening for proteins that interact with alpha1-adrenergic receptors . Acta Pharmacologica Sinica . 25 . 11 . 1471–1478 . November 2004 . 15525470 .
• Sigala S, Dellabella M, Milanese G, Fornari S, Faccoli S, Palazzolo F, Peroni A, Mirabella G, Cunico SC, Spano P, Muzzonigro G . Evidence for the presence of alpha1 adrenoceptor subtypes in the human ureter . Neurourology and Urodynamics . 24 . 2 . 142–148 . 2005 . 15690361 . 10.1002/nau.20097 . 23187341 .
• Chen Z, Hague C, Hall RA, Minneman KP . Syntrophins regulate alpha1D-adrenergic receptors through a PDZ domain-mediated interaction . The Journal of Biological Chemistry . 281 . 18 . 12414–12420 . May 2006 . 16533813 . 10.1074/jbc.M508651200 . free .
• Michelotti GA, Brinkley DM, Morris DP, Smith MP, Louie RJ, Schwinn DA . Epigenetic regulation of human alpha1d-adrenergic receptor gene expression: a role for DNA methylation in Sp1-dependent regulation . FASEB Journal . 21 . 9 . 1979–1993 . July 2007 . 17384146 . 2279228 . 10.1096/fj.06-7118com . free .

Notes and References

1. Web site: Entrez Gene: ADRA1D adrenergic, alpha-1D-, receptor.
2. Buckner SA, Milicic I, Daza A, Lynch JJ, Kolasa T, Nakane M, Sullivan JP, Brioni JD . A-315456: a selective alpha(1D)-adrenoceptor antagonist with minimal dopamine D(2) and 5-HT(1A) receptor affinity . European Journal of Pharmacology . 433 . 1 . 123–127 . December 2001 . 11755142 . 10.1016/s0014-2999(01)01519-9 .
3. Cleary L, Murad K, Bexis S, Docherty JR . The alpha (1D)-adrenoceptor antagonist BMY 7378 is also an alpha (2C)-adrenoceptor antagonist . Autonomic & Autacoid Pharmacology . 25 . 4 . 135–141 . October 2005 . 16176444 . 10.1111/j.1474-8673.2005.00342.x .
4. Indra B, Matsunaga K, Hoshino O, Suzuki M, Ogasawara H, Muramatsu I, Taniguchi T, Ohizumi Y . (+/-)-Domesticine, a novel and selective alpha1D-adrenoceptor antagonist in animal tissues and human alpha 1-adrenoceptors . European Journal of Pharmacology . 445 . 1-2 . 21–29 . June 2002 . 12065190 . 10.1016/s0014-2999(02)01601-1 .
5. Proudman RG, Pupo AS, Baker JG . The affinity and selectivity of α-adrenoceptor antagonists, antidepressants, and antipsychotics for the human α1A, α1B, and α1D-adrenoceptors . Pharmacology Research & Perspectives . 8 . 4 . e00602 . August 2020 . 32608144 . 7327383 . 10.1002/prp2.602 .