Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites

Nature

Volumn 444, Issue 7118, 2006, Pages 486-489

  Hosie, Alastair M ^a   Wilkins, Megan E ^a   Da Silva, Helena M A ^a   Smart, Trevor G ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN; ETHANOL; HORMONES; PHYSIOLOGY; STRESS ANALYSIS; SYNTHESIS (CHEMICAL);

ALLOPREGNANOLONE; ETHANOL CONSUMPTION; NEUROSTEROIDS; TRANSMEMBRANE SITES;

GENETIC ENGINEERING;

3ALPHA HYDROXY 5ALPHA PREGNAN 20 ONE; 4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; ALCOHOL; DEOXYCORTICOSTERONE; NEUROSTEROID;

BRAIN; PHYSIOLOGY; STEROID;

ALCOHOL CONSUMPTION; ALCOHOLISM; ALPHA CHAIN; ARTICLE; BETA CHAIN; BINDING SITE; CATAMENIAL EPILEPSY; GABAERGIC TRANSMISSION; HUMAN; HUMAN CELL; MAJOR DEPRESSION; MOUSE; NEUROTRANSMISSION; NONHUMAN; PANIC; PREGNANCY; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FAMILY; RECEPTOR UPREGULATION; REGULATORY MECHANISM; SCHIZOPHRENIA; STEROIDOGENESIS; STRESS;

EID: 33751314737     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature05324     Document Type: Article

References (28)

1. A receptor. Nature Rev. Neurosci. 6, 565-575 (2005).
2. Reddy, D. S. Is there a physiological role for the neurosteroid THDOC in stress-sensitive conditions? Trends Pharmacol. Sci. 24, 103-106 (2003).
3. Stoffel-Wagner, B. Neurosteroid biosynthesis in the human brain and its clinical implications. Ann. NY Acad. Sci. 1007, 64-78 (2003).
4. Kumar, S., Fleming, R. L. & Morrow, A. L. Ethanol regulation of gamma-aminobutyric acid A receptors: genomic and nongenomic mechanisms. Pharmacol. Ther. 101, 211-226 (2004).
5. Backstrom, T. et al. Pathogenesis in menstrual cycle-linked CNS disorders. Ann. NY Acad. Sci. 1007, 42-53 (2003).
6. Finn, D. A., Ford, M. M., Wiren, K. M., Roselli, C. E. & Crabbe, J. C. The role of pregnane neurosteroids in ethanol withdrawal: behavioral genetic approaches. Pharmacol. Ther. 101, 91-112 (2004).
7. Eser, D. et al. Neuroactive steroids as modulators of depression and anxiety. Neuroscience 138, 1041-1048 (2006).
8. Marx, C. E. et al. Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics. Neuropsychopharmacology 31, 1249-1263 (2006).
9. Fritschy, J. M. & Brunig, I. Formation and plasticity of GABAergic synapses: physiological mechanisms and pathophysiological implications. Pharmacol. Ther. 98, 299-323 (2003).
10. Purdy, R. H., Morrow, A. L., Moore, P. H. Jr & Paul, S. M. Stress-induced elevations of c-aminobutyric acid type A receptor-active steroids in the rat brain. Proc. Natl Acad. Sci. USA 88, 4553-4557 (1991).
11. Barbaccia, M. L. et al. The effects of inhibitors of GABAergic transmission and stress on brain and plasma allopregnanolone concentrations. Br. J. Pharmacol. 120, 1582-1588 (1997).
12. A channel deactivation by altering kinetics of desensitized states. J. Neurosci. 17, 4022-4031 (1997).
13. Stell, B. M., Brickley, S. G., Tang, C. Y., Farrant, M. & Mody, I. Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by δ subunit-containing GABAA receptors. Proc. Natl Acad. Sci. USA 100, 14439-14444 (2003).
14. A receptor-mediated inhibitory neurotransmission in the rat hippocampus: evidence for endogenous neurosteroids? J. Neurosci. 23, 10013-10020 (2003).
15. Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L. & Paul, S. M. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 232, 1004-1007 (1986).
16. A receptor at sites on the N-terminal side of the middle of TM2. Neuroreport 9, 379-383 (1998).
17. A receptor. J. Neurosci. 25, 11605-11613 (2005).
18. Ueno, S., Tsutsui, M., Toyohira, Y., Minami, K. & Yanagihara, N. Sites of positive allosteric modulation by neurosteroids on ionotropic gamma-aminobutyric acid receptor subunits. FEBS Lett. 566, 213-217 (2004).
19. Chen, R. et al. Cloning and functional expression of a Drosophila γ-aminobutyric acid receptor. Proc. Natl Acad. Sci. USA 91, 6069-6073 (1994).
20. Harrison, N. L., Majewska, M. D., Harrington, J. W. & Barker, J. L. Structure-activity relationships for steroid interaction with the gamma-aminobutyric acid-A receptor complex. J. Pharmacol. Exp. Ther. 241, 346-353 (1987).
21. Grishkovskaya, I. et al. Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain. EMBO J. 19, 504-512 (2000).
22. Brzozowski, A. M. et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389, 753-758 (1997).
23. Miyazawa, A., Fujiyoshi, Y. & Unwin, N. Structure and gating mechanism of the acetylcholine receptor pore. Nature 423, 949-955 (2003).
24. Williams, D. B. & Akabas, M. H. γ-Aminobutyric acid increases the water accessibility of M3 membrane-spanning segment residues in γ-aminobutyric acid type A receptors. Biophys. J. 77, 2563-2574 (1999).
25. Lobo, I. A., Mascia, M. P., Trudell, J. R. & Harris, R. A. Channel gating of the glycine receptor changes accessibility to residues implicated in receptor potentiation by alcohols and anesthetics. J. Biol. Chem. 279, 33919-33927 (2004).
26. A receptor α1 subunit during channel gating and alcohol modulation. J. Biol. Chem. 280, 308-316 (2005).
27. Schwede, T., Kopp, J., Guex, N. & Peitsch, M. C. SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res. 31, 3381-3385 (2003).
28. A α1 receptor using three crystal structures as templates. J. Mol. Graph. Model. 23, 39-49 (2004).