Beta-3 adrenergic receptor
The beta-3 adrenergic receptor (β3-adrenoceptor), also known as ADRB3, is a
Function
Actions of the β3 receptor include
- Enhancement of lipolysis in adipose tissue.[6]
- Thermogenesis in skeletal muscle[7]
It is located mainly in
antistress effects in animal studies, suggesting it also has a role in the central nervous system (CNS). β3 receptors are found in the gallbladder, urinary bladder, and in brown adipose tissue. Their role in gallbladder physiology is unknown, but they are thought to play a role in lipolysis and thermogenesis in brown fat. In the urinary bladder it is thought to cause relaxation of the bladder and prevention of urination.[8]
Mechanism of action
Beta adrenergic receptors are involved in the
Ligands
Agonists
- Amibegron (SR-58611A)[9][10]
- BRL-37344[11]
- CL-316,243[12]
- L-742,791[13]
- L-796,568[14]
- LY-368,842
- Mirabegron (YM-178),[15] approved for treatment of overactive bladder in Japan, United States, UK, Canada, China and India.
- Nebivolol[16] selective beta(1)-blocker and beta(3)-agonist.
- Ro40-2148
- Solabegron (GW-427,353)[17]
- Vibegron (MK-4618)[18]
Antagonists
- L-748,328[13]
- L-748,337[13]
- SR 59230A was thought to be a selective β3 antagonist[19] but later found to also be an antagonist of the α1 receptor.[20]
Interactions
Beta-3 adrenergic receptor has been shown to
Src.[21]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000188778 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031489 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: ADRB3 adrenergic, beta-3-, receptor".
- PMID 15935402.
- ISBN 0-443-07145-4. Page 163
- PMID 16457637.
- PMID 17669397.
- S2CID 35026036.
- PMID 30892909.
- PMID 18304529.
- ^ PMID 10411574.
- PMID 12324291.
- PMID 22384458.
- PMID 19389564.
- S2CID 19281697.
- PMID 26709102.
- PMID 8569714.
- PMID 19422394.
- PMID 11013230.
Further reading
- Granneman JG, Lahners KN, Rao DD (1993). "Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block". Mol. Pharmacol. 42 (6): 964–70. PMID 1336117.
- Nahmias C, Blin N, Elalouf JM, Mattei MG, Strosberg AD, Emorine LJ (1991). "Molecular characterization of the mouse beta 3-adrenergic receptor: relationship with the atypical receptor of adipocytes". EMBO J. 10 (12): 3721–7. PMID 1718744.
- Emorine LJ, Marullo S, Briend-Sutren MM, Patey G, Tate K, Delavier-Klutchko C, Strosberg AD (1989). "Molecular characterization of the human beta 3-adrenergic receptor". Science. 245 (4922): 1118–21. PMID 2570461.
- Guan XM, Amend A, Strader CD (1995). "Determination of structural domains for G protein coupling and ligand binding in beta 3-adrenergic receptor". Mol. Pharmacol. 48 (3): 492–8. PMID 7565630.
- Rodriguez M, Carillon C, Coquerel A, Le Fur G, Ferrara P, Caput D, Shire D (1995). "Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain". Brain Res. Mol. Brain Res. 29 (2): 369–75. PMID 7609625.
- Clément K, Vaisse C, Manning BS, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosberg AD (1995). "Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity". N. Engl. J. Med. 333 (6): 352–4. PMID 7609752.
- Dib A, Adélaïde J, Chaffanet M, Imbert A, Le Paslier D, Jacquemier J, Gaudray P, Theillet C, Birnbaum D, Pébusque MJ (1995). "Characterization of the region of the short arm of chromosome 8 amplified in breast carcinoma". Oncogene. 10 (5): 995–1001. PMID 7898940.
- Mahmoudian M (1994). "The complex of human Gs protein with the beta 3 adrenergic receptor: a computer-aided molecular modeling study". Journal of Molecular Graphics. 12 (1): 22–8, 34. PMID 8011597.
- Wilkie TM, Chen Y, Gilbert DJ, Moore KJ, Yu L, Simon MI, Copeland NG, Jenkins NA (1994). "Identification, chromosomal location, and genome organization of mammalian G-protein-coupled receptors". Genomics. 18 (2): 175–84. PMID 8288218.
- Krief S, Lönnqvist F, Raimbault S, Baude B, Van Spronsen A, Arner P, Strosberg AD, Ricquier D, Emorine LJ (1993). "Tissue distribution of beta 3-adrenergic receptor mRNA in man". J. Clin. Invest. 91 (1): 344–9. PMID 8380813.
- van Spronsen A, Nahmias C, Krief S, Briend-Sutren MM, Strosberg AD, Emorine LJ (1993). "The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes". Eur. J. Biochem. 213 (3): 1117–24. PMID 8389293.
- Lelias JM, Kaghad M, Rodriguez M, Chalon P, Bonnin J, Dupre I, Delpech B, Bensaid M, LeFur G, Ferrara P (1993). "Molecular cloning of a human beta 3-adrenergic receptor cDNA". FEBS Lett. 324 (2): 127–30. S2CID 84702667.
- Candelore MR, Deng L, Tota LM, Kelly LJ, Cascieri MA, Strader CD (1996). "Pharmacological characterization of a recently described human beta 3-adrenergic receptor mutant". Endocrinology. 137 (6): 2638–41. PMID 8641219.
- Fujisawa T, Ikegami H, Yamato E, Takekawa K, Nakagawa Y, Hamada Y, Oga T, Ueda H, Shintani M, Fukuda M, Ogihara T (1996). "Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain". Diabetologia. 39 (3): 349–52. S2CID 24270803.
- Higashi K, Ishikawa T, Ito T, Yonemura A, Shige H, Nakamura H (1997). "Association of a genetic variation in the beta 3-adrenergic receptor gene with coronary heart disease among Japanese". Biochem. Biophys. Res. Commun. 232 (3): 728–30. PMID 9126344.
- Hoffstedt J, Poirier O, Thörne A, Lönnqvist F, Herrmann SM, Cambien F, Arner P (1999). "Polymorphism of the human beta3-adrenoceptor gene forms a well-conserved haplotype that is associated with moderate obesity and altered receptor function". Diabetes. 48 (1): 203–5. PMID 9892244.
- Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A (1999). "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis". Nat. Genet. 22 (3): 239–47. S2CID 4636523.
- Kimura K, Sasaki N, Asano A, Mizukami J, Kayahashi S, Kawada T, Fushiki T, Morimatsu M, Yoshida T, Saito M (2000). "Mutated human beta3-adrenergic receptor (Trp64Arg) lowers the response to beta3-adrenergic agonists in transfected 3T3-L1 preadipocytes". Horm. Metab. Res. 32 (3): 91–6. S2CID 260166451.
- Cao W, Luttrell LM, Medvedev AV, Pierce KL, Daniel KW, Dixon TM, Lefkowitz RJ, Collins S (2001). "Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation". J. Biol. Chem. 275 (49): 38131–4. PMID 11013230.
- Russell ST, Hirai K, Tisdale MJ (2002). "Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor". Br. J. Cancer. 86 (3): 424–8. PMID 11875710.
External links
- "β3-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 30 December 2014. Retrieved 25 November 2008.
- Human ADRB3 genome location and ADRB3 gene details page in the UCSC Genome Browser.