| 释义 |
- Function
- Subunit selective ligands Agonists Inverse agonists
- See also
- References
- Further reading
- External links
{{Infobox_gene}}Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the GABRA5 gene.[1][2]FunctionGABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABAA receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABAA receptor. At least 16 distinct subunits of GABAA receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described.[1]Subunit selective ligandsRecent research has produced several ligands which are moderately selective for GABAA receptors containing the α5 subunit. These have proved to be useful in investigating some of the side effects of benzodiazepine and nonbenzodiazepine drugs, particularly the effects on learning and memory such as anterograde amnesia. Inverse agonists at this subunit have nootropic effects and may be useful for the treatment of cognitive disorders such as Alzheimer's disease. Agonists- QH-ii-066
- SH-053-R-CH3-2′F
Inverse agonists- α5IA
- Basmisanil (RG-1662, RO5186582): derivative of Ro4938581, negative allosteric modulator at GABAA α5, in human trials for treating cognitive deficit in Down syndrome.[3]
- L-655,708
- MRK-016
- PWZ-029: moderate inverse agonist[4]
- Pyridazines[5]
- Ro4938581[6]
- TB-21007[7][8]
See alsoReferences1. ^1 {{cite web | title = Entrez Gene: GABRA5 gamma-aminobutyric acid (GABA) A receptor, alpha 5| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2558| accessdate = }}
2. ^{{cite journal |vauthors=Wingrove P, Hadingham K, Wafford K, Kemp JA, Ragan CI, Whiting P | title = Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit | journal = Biochem. Soc. Trans. | volume = 20 | issue = 1 | pages = 18S |date=February 1992 | pmid = 1321750 | doi = | url = | issn = }}
3. ^{{Cite journal | last1 = McCabe | first1 = L. L. | last2 = McCabe | first2 = E. R. B. | doi = 10.1111/cga.12000 | title = Down syndrome and personalized medicine: Changing paradigms from genotype to phenotype to treatment | journal = Congenital Anomalies | volume = 53 | issue = 1 | pages = 1–2 | year = 2013 | pmid = 23480351| pmc = }}
4. ^{{cite journal |vauthors=Savić MM, Clayton T, Furtmüller R |title=PWZ-029, a compound with moderate inverse agonist functional selectivity at GABA(A) receptors containing alpha5 subunits, improves passive, but not active, avoidance learning in rats |journal=Brain Res. |volume=1208 |issue= |pages=150–9 |year=2008 |pmid=18394590 |pmc=2577822 |doi=10.1016/j.brainres.2008.02.020 |url=|display-authors=etal}}
5. ^{{cite journal |vauthors=van Niel MB, Wilson K, Adkins CH |title=A new pyridazine series of GABAA alpha5 ligands |journal=J. Med. Chem. |volume=48 |issue=19 |pages=6004–11 |year=2005 |pmid=16162003 |doi=10.1021/jm050249x |url=|display-authors=etal}}
6. ^{{cite journal |vauthors=Ballard TM, Knoflach F, Prinssen E |title=RO4938581, a novel cognitive enhancer acting at GABA(A) alpha5 subunit-containing receptors |journal=Psychopharmacology |volume= 202|issue= 1–3|pages= 207–23|year=2008 |pmid=18936916 |doi=10.1007/s00213-008-1357-7 |url=|display-authors=etal}}
7. ^{{cite journal |vauthors=Chambers MS, Atack JR, Bromidge FA |title=6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists |journal=J. Med. Chem. |volume=45 |issue=6 |pages=1176–9 |year=2002 |pmid=11881985|doi=10.1021/jm010471b|display-authors=etal}}
8. ^{{cite journal |vauthors=Chambers MS, Atack JR, Broughton HB |title=Identification of a novel, selective GABA(A) alpha5 receptor inverse agonist which enhances cognition |journal=J. Med. Chem. |volume=46 |issue=11 |pages=2227–40 |year=2003 |pmid=12747794 |doi=10.1021/jm020582q |url=|display-authors=etal}}
Further reading{{refbegin | 2}}- {{cite journal | author=Delong R |title=GABA(A) receptor alpha5 subunit as a candidate gene for autism and bipolar disorder: a proposed endophenotype with parent-of-origin and gain-of-function features, with or without oculocutaneous albinism |journal=Autism |volume=11 |issue= 2 |pages= 135–47 |year= 2007 |pmid= 17353214 |doi= 10.1177/1362361307075705 }}
- {{cite journal |vauthors=Otani K, Ujike H, Tanaka Y |title=The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder |journal=Neurosci. Lett. |volume=381 |issue= 1–2 |pages= 108–13 |year= 2005 |pmid= 15882799 |doi= 10.1016/j.neulet.2005.02.010 |display-authors=etal}}
- {{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}}
- {{cite journal | author=Chou KC |title=Modelling extracellular domains of GABA-A receptors: subtypes 1, 2, 3, and 5 |journal=Biochem. Biophys. Res. Commun. |volume=316 |issue= 3 |pages= 636–42 |year= 2004 |pmid= 15033447 |doi= 10.1016/j.bbrc.2004.02.098 }}
- {{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |display-authors=etal}}
- {{cite journal |vauthors=Ritchie RJ, Mattei MG, Lalande M |title=A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications |journal=Hum. Mol. Genet. |volume=7 |issue= 8 |pages= 1253–60 |year= 1998 |pmid= 9668167 |doi=10.1093/hmg/7.8.1253 }}
- {{cite journal |vauthors=Kim Y, Glatt H, Xie W |title=Human gamma-aminobutyric acid-type A receptor alpha5 subunit gene (GABRA5): characterization and structural organization of the 5' flanking region |journal=Genomics |volume=42 |issue= 3 |pages= 378–87 |year= 1997 |pmid= 9205108 |doi= 10.1006/geno.1997.4770 |display-authors=etal}}
- {{cite journal |vauthors=Glatt K, Glatt H, Lalande M |title=Structure and organization of GABRB3 and GABRA5 |journal=Genomics |volume=41 |issue= 1 |pages= 63–9 |year= 1997 |pmid= 9126483 |doi= 10.1006/geno.1997.4639 }}
- {{cite journal |vauthors=Knoll JH, Sinnett D, Wagstaff J |title=FISH ordering of reference markers and of the gene for the alpha 5 subunit of the gamma-aminobutyric acid receptor (GABRA5) within the Angelman and Prader–Willi syndrome chromosomal regions |journal=Hum. Mol. Genet. |volume=2 |issue= 2 |pages= 183–9 |year= 1993 |pmid= 8388764 |doi=10.1093/hmg/2.2.183 |display-authors=etal}}
- {{cite journal |vauthors=Russek SJ, Farb DH |title=Mapping of the beta 2 subunit gene (GABRB2) to microdissected human chromosome 5q34-q35 defines a gene cluster for the most abundant GABAA receptor isoform |journal=Genomics |volume=23 |issue= 3 |pages= 528–33 |year= 1995 |pmid= 7851879 |doi= 10.1006/geno.1994.1539 }}
- {{cite journal |vauthors=Glatt KA, Sinnett D, Lalande M |title=Dinucleotide repeat polymorphism at the GABAA receptor alpha 5 (GABRA5) locus at chromosome 15q11-q13 |journal=Hum. Mol. Genet. |volume=1 |issue= 5 |pages= 348 |year= 1993 |pmid= 1338907 |doi=10.1093/hmg/1.5.348 }}
- {{cite journal |vauthors=Wingrove P, Hadingham K, Wafford K |title=Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit |journal=Biochem. Soc. Trans. |volume=20 |issue= 1 |pages= 18S |year= 1992 |pmid= 1321750 |doi= |display-authors=etal}}
{{refend}}External links- {{MeshName|GABRA5+protein,+human}}
{{NLM content}}{{Ligand-gated ion channels}}{{GABAergics}}{{membrane-protein-stub}} 2 : Ion channels|Biology of bipolar disorder |