GABAA-rho receptor
gamma-aminobutyric acid (GABA) receptor, rho 1 | |||||||
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Identifiers | |||||||
Symbol | GABRR1 | ||||||
NCBI gene | 2569 | ||||||
HGNC | 4090 | ||||||
OMIM | 137161 | ||||||
RefSeq | NM_002042 | ||||||
UniProt | P24046 | ||||||
Other data | |||||||
Locus | Chr. 6 q14-q21 | ||||||
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gamma-aminobutyric acid (GABA) receptor, rho 2 | |||||||
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Identifiers | |||||||
Symbol | GABRR2 | ||||||
NCBI gene | 2570 | ||||||
HGNC | 4091 | ||||||
OMIM | 137162 | ||||||
RefSeq | NM_002043 | ||||||
UniProt | P28476 | ||||||
Other data | |||||||
Locus | Chr. 6 q14-q21 | ||||||
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gamma-aminobutyric acid (GABA) receptor, rho 3 | |||||||
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Identifiers | |||||||
Symbol | GABRR3 | ||||||
NCBI gene | 200959 | ||||||
HGNC | 17969 | ||||||
RefSeq | NM_001105580 | ||||||
UniProt | Q9UIV9 | ||||||
Other data | |||||||
Locus | Chr. 3 q12.2 | ||||||
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The GABAA-rho receptor (previously known as the GABAC receptor) is a subclass of GABAA receptors composed entirely of rho (
Nomenclature
[edit]A second type of ionotropic GABA receptor, insensitive to typical allosteric modulators of GABAA receptor channels such as benzodiazepines and barbiturates,[2][3][4] was designated GABAС receptor.[5][6] Native responses of the GABAC receptor type occur in retinal bipolar or horizontal cells across vertebrate species.[7][8][9][10]
GABAС receptors are exclusively composed of
Function
[edit]In addition to containing a GABA binding site, the GABAA-
Structure
[edit]Like other ligand-gated ion channels, the GABAA-
The above three subunits coassemble either to form functional homo-pentamers (
There is also evidence that
Pharmacology
[edit]There are several pharmacological differences that distinguish GABAA-
- selectively activated by (+)-CAMP [(+)-cis-2-aminomethylcyclopropane-carboxylic acid] and blocked by TPMPA [(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid];
- not sensitive to the GABAB agonist baclofen nor the GABAA receptor antagonist bicuculline;
- not modulated by many GABAA receptor modulators such as barbiturates and benzodiazepines, but are modulated selectively by certain neuroactive steroids.[25]
Selective Ligands
[edit]Agonists
[edit]Antagonists
[edit]- Mixed GABAA-
ρ / GABAB antagonists
- ZAPA ((Z)-3-[(Aminoiminomethyl)thio]prop-2-enoic acid)
- SKF-97541 (3-Aminopropyl(methyl)phosphinic acid)
- CGP-36742 (3-aminopropyl-n-butyl-phosphinic acid)
- Selective GABAA-
ρ antagonists
- TPMPA
- (±)-cis-(3-Aminocyclopentyl)butylphosphinic acid
- (S)-(4-Aminocyclopent-1-enyl)butylphosphinic acid
- N2O
Genetics
[edit]In humans, GABAA-
References
[edit]- ^ Qian H. 2000. GABAc receptors in the vertebrate retina Archived 2010-12-31 at the Wayback Machine. Retrieved on February 14, 2007.
- ^ Sivilotti L, Nistri A (1991). "GABA receptor mechanisms in the central nervous system". Prog. Neurobiol. 36 (1): 35–92. doi:10.1016/0301-0082(91)90036-Z. PMID 1847747. S2CID 31732465.
- ^ Bormann J, Feigenspan A (December 1995). "GABAC receptors". Trends Neurosci. 18 (12): 515–519. doi:10.1016/0166-2236(95)98370-E. PMID 8638289. S2CID 40853254.
- ^ Johnston GA (September 1996). "GABAc receptors: relatively simple transmitter -gated ion channels?". Trends Pharmacol. Sci. 17 (9): 319–323. doi:10.1016/0165-6147(96)10038-9. PMID 8885697.
- ^ Drew CA, Johnston GA, Weatherby RP (December 1984). "Bicuculline-insensitive GABA receptors: studies on the binding of (−)-baclofen to rat cerebellar membranes". Neurosci. Lett. 52 (3): 317–321. doi:10.1016/0304-3940(84)90181-2. PMID 6097844. S2CID 966075.
- ^ Zhang D, Pan ZH, Awobuluyi M, Lipton SA (March 2001). "Structure and function of GABAC receptors: a comparison of native versus recombinant receptors". Trends Pharmacol. Sci. 22 (3): 121–132. doi:10.1016/S0165-6147(00)01625-4. PMID 11239575.
- ^ Feigenspan A, Wässle H, Bormann J (January 1993). "Pharmacology of GABA receptor Cl− channels in rat retinal bipolar cells". Nature. 361 (6408): 159–162. Bibcode:1993Natur.361..159F. doi:10.1038/361159a0. PMID 7678450. S2CID 4347233.
- ^ Qian H, Dowling JE (January 1993). "Novel GABA responses from rod-driven retinal horizontal cells". Nature. 361 (6408): 162–164. Bibcode:1993Natur.361..162Q. doi:10.1038/361162a0. PMID 8421521. S2CID 4320616.
- ^ Lukasiewicz PD (June 1996). "GABAC receptors in the vertebrate retina". Mol. Neurobiol. 12 (3): 181–194. doi:10.1007/BF02755587. PMID 8884747. S2CID 37167159.
- ^ Wegelius K, Pasternack M, Hiltunen JO, Rivera C, Kaila K, Saarma M, Reeben M (January 1998). "Distribution of GABA receptor rho subunit transcripts in the rat brain". Eur. J. Neurosci. 10 (1): 350–357. doi:10.1046/j.1460-9568.1998.00023.x. PMID 9753143. S2CID 25863134.
- ^ Shimada S, Cutting G, Uhl GR (April 1992). "gamma-Aminobutyric acid A or C receptor? gamma-Aminobutyric acid rho 1 receptor RNA induces bicuculline-, barbiturate-, and benzodiazepine-insensitive gamma-aminobutyric acid responses in Xenopus oocytes". Mol. Pharmacol. 41 (4): 683–687. PMID 1314944.
- ^ Kusama T, Spivak CE, Whiting P, Dawson VL, Schaeffer JC, Uhl GR (May 1993). "Pharmacology of GABA
ρ 1 and GABAα /β receptors expressed in Xenopus oocytes and COS cells". Br. J. Pharmacol. 109 (1): 200–206. doi:10.1111/j.1476-5381.1993.tb13554.x. PMC 2175610. PMID 8388298. - ^ Kusama T, Wang TL, Guggino WB, Cutting GR, Uhl GR (March 1993). "GABA rho 2 receptor pharmacological profile: GABA recognition site similarities to rho 1". Eur. J. Pharmacol. 245 (1): 83–84. doi:10.1016/0922-4106(93)90174-8. PMID 8386671.
- ^ Barnard EA, Skolnick P, Olsen RW, Mohler H, Sieghart W, Biggio G, Braestrup C, Bateson AN, Langer SZ (June 1998). "International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function". Pharmacol. Rev. 50 (2): 291–313. PMID 9647870.
- ^ Chebib M, Johnston GA (April 2000). "GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology". J. Med. Chem. 43 (8): 1427–1447. doi:10.1021/jm9904349. PMID 10780899.
- ^ Bormann J (January 2000). "The 'ABC' of GABA receptors". Trends Pharmacol. Sci. 21 (1): 16–19. doi:10.1016/S0165-6147(99)01413-3. PMID 10637650.
- ^ Olsen RW, Sieghart W (September 2008). "International Union of Pharmacology. LXX. Subtypes of gamma-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. Update". Pharmacological Reviews. 60 (3): 243–260. doi:10.1124/pr.108.00505. PMC 2847512. PMID 18790874.
- ^ Enz R, Cutting GR (1998). "Molecular composition of GABAC receptors". Vision Res. 38 (10): 1431–1441. doi:10.1016/S0042-6989(97)00277-0. PMID 9667009. S2CID 14457042.
- ^ Ogurusu T, Yanagi K, Watanabe M, Fukaya M, Shingai R (1999). "Localization of GABA receptor rho 2 and rho 3 subunits in rat brain and functional expression of homo-oligomeric rho 3 receptors and hetero-oligomeric rho 2 rho 3 receptors". Receptors Channels. 6 (6): 463–475. PMID 10635063.
- ^ Qian H, Ripps H (1999). "Response kinetics and pharmacological properties of heteromeric receptors formed by coassembly of GABA
ρ - andγ 2-subunits". Proceedings of the Royal Society B. 266 (1436): 2419–2425. doi:10.1098/rspb.1999.0941. PMC 1690471. PMID 10643085. - ^ Milligan CJ, Buckley NJ, Garret M, Deuchars J, Deuchars SA (August 2004). "Evidence for inhibition mediated by coassembly of GABAA and GABAC receptor subunits in native central neurons". Journal of Neuroscience. 24 (33): 7241–7250. doi:10.1523/JNEUROSCI.1979-04.2004. PMC 6729776. PMID 15317850.
- ^ Pan Y, Qian H (July 2005). "Interactions between rho and gamma2 subunits of the GABA receptor". Journal of Neurochemistry. 94 (2): 482–490. doi:10.1111/j.1471-4159.2005.03225.x. PMID 15998298. S2CID 19865977.
- ^ Sieghart W, Ernst M (2005). "Heterogeneity of GABAA receptors: Revived interest in the development of subtype-selective drugs". Current Medicinal Chemistry. 5 (3): 217–242. doi:10.2174/1568015054863837.
- ^ Chebib M, Johnston GA (2000). "GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology". J Med Chem. 43 (8): 1427–1447. doi:10.1021/jm9904349. PMID 10780899.
- ^ Morris KD, Moorefield CN, Amin J. Differential modulation of the gamma-aminobutyric acid type C receptor by neuroactive steroids. Mol Pharmacol. 1999;56(4):752‐759
- ^ Hinton T, Chebib M, Johnston GA (January 2008). "Enantioselective actions of 4-amino-3-hydroxybutanoic acid and (3-amino-2-hydroxypropyl)methylphosphinic acid at recombinant GABA(C) receptors". Bioorganic & Medicinal Chemistry Letters. 18 (1): 402–404. doi:10.1016/j.bmcl.2007.10.019. PMID 17981464.
- ^ Marcos I, Ruiz A, Blaschak CJ, Borrego S, Cutting GR, Antinolo G (1998). "Mutation analysis of GABRR1 and GABRR2 in autosomal recessive retinitis pigmentosa". J Med Genet. 37 (6): E5. doi:10.1136/jmg.37.6.e5. PMC 1734609. PMID 10851258.