Dihydropyrimidinone positive modulation of δ-subunit-containing γ-aminobutyric acid type a receptors, including an epilepsy-linked mutant variant

Biochemistry

Volumn 49, Issue 23, 2010, Pages 4841-4851

  Lewis, Ryan W ^a   Mabry, John ^a   Polisar, Jason G ^a   Eagen, Kyle P ^a   Ganem, Bruce ^a,b   Hess, George P ^a  

^a Department of Obstetrics Gynecology   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AGONIST ACTIVITY; AMINOBUTYRIC ACIDS; BIGINELLI REACTION; CENTRAL NERVOUS SYSTEMS; CHLORIDE CHANNELS; DISSOCIATION CONSTANT; DOSE-DEPENDENT; HETEROCYCLES; KINETIC MODELS; MONASTROL; PEAK CURRENTS; RESEARCH TOOLS; SIGNAL TRANSMISSION; STRUCTURAL FEATURE; THERAPEUTIC AGENTS; THREE-COMPONENT;

ACIDS; CHLORINE COMPOUNDS; DISSOCIATION; MAMMALS;

AMINO ACIDS;

4 AMINOBUTYRIC ACID A RECEPTOR; DIHYDROPYRIMIDINONE; JGP 1 80A; JGP I 142C; JGP I 150B; JGP I 151B; JGP II 17F; JGP II 28K; JM II 43A; JM III 12A; JM III 14A; JM III 3; JM III 4B; JM III 6A; MONASTROL; PHENOBARBITAL; PYRIMIDINONE DERIVATIVE; RECOMBINANT RECEPTOR; TRACAZOLATE; UNCLASSIFIED DRUG;

AMPLITUDE MODULATION; ARTICLE; BIGINELLI REACTION; CHEMICAL STRUCTURE; DISSOCIATION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; RECEPTOR POTENTIAL; RECEPTOR SENSITIVITY; STRUCTURE ANALYSIS; SYNTHESIS;

ALANINE; ALLOSTERIC REGULATION; CELL LINE; DRUG SYNERGISM; EPILEPSY; GENETIC VARIATION; GLUTAMIC ACID; HUMANS; MUTAGENESIS, SITE-DIRECTED; PROTEIN BINDING; PROTEIN ISOFORMS; PROTEIN SUBUNITS; PYRIMIDINES; PYRIMIDINONES; RECEPTORS, GABA-A; THIONES;

MAMMALIA;

EID: 77953254431     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi100119t     Document Type: Article

References (62)

1. Mehta, A. K. and Ticku, M. K. (1999) An update on GABAA receptors Brain Res. Brain Res. Rev. 29, 196-217
2. Sieghart, W. (2006) Structure, pharmacology, and function of GABAA receptor subtypes Adv. Pharmacol. 54, 231-263
3. Johnston, G. A. (1996) GABAA receptor pharmacology Pharmacol. Ther. 69, 173-198
4. Olsen, R. W. and Sieghart, W. (2009) GABAA receptors: Subtypes provide diversity of function and pharmacology Neuropharmacology 56, 141-148
5. Saxena, N. C. and Macdonald, R. L. (1994) Assembly of GABAA receptor subunits: Role of the δ subunit J. Neurosci. 14, 7077-7086
6. Mohler, H., Benke, D., Benson, J., Luscher, B., and Fritschy, J. M. (1995) GABAA-receptor subtypes in vivo: Cellular localization, pharmacology and regulation Adv. Biochem. Psychopharmacol. 48, 41-56
7. Nusser, Z., Sieghart, W., and Somogyi, P. (1998) Segregation of different GABAA receptors to synaptic and extrasynaptic membranes of cerebellar granule cells J. Neurosci. 18, 1693-1703
8. Zheleznova, N., Sedelnikova, A., and Weiss, D. S. (2008) α1β2δ, a silent GABAA receptor: Recruitment by tracazolate and neurosteroids Br. J. Pharmacol. 153, 1062-1071
9. Spigelman, I., Li, Z., Banerjee, P. K., Mihalek, R. M., Homanics, G. E., and Olsen, R. W. (2002) Behavior and physiology of mice lacking the GABAA-receptor δ subunit Epilepsia 43 (Suppl. 5) 3-8
10. Mihalek, R. M., Banerjee, P. K., Korpi, E. R., Quinlan, J. J., Firestone, L. L., Mi, Z. P., Lagenaur, C., Tretter, V., Sieghart, W., Anagnostaras, S. G., Sage, J. R., Fanselow, M. S., Guidotti, A., Spigelman, I., Li, Z., DeLorey, T. M., Olsen, R. W., and Homanics, G. E. (1999) Attenuated sensitivity to neuroactive steroids in γ-aminobutyrate type A receptor δ subunit knockout mice Proc. Natl. Acad. Sci. U.S.A. 96, 12905-12910
11. Macdonald, R. L. and Kang, J. Q. (2009) Molecular pathology of genetic epilepsies associated with GABA(A) receptor subunit mutations Epilepsy Curr. 9, 18-23
12. Dibbens, L. M., Feng, H. J., Richards, M. C., Harkin, L. A., Hodgson, B. L., Scott, D., Jenkins, M., Petrou, S., Sutherland, G. R., Scheffer, I. E., Berkovic, S. F., Macdonald, R. L., and Mulley, J. C. (2004) GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies Hum. Mol. Genet. 13, 1315-1319
13. Macdonald, R. L., Gallagher, M. J., Feng, H. J., and Kang, J. (2004) GABA(A) receptor epilepsy mutations Biochem. Pharmacol. 68, 1497-1506
14. Feng, H. J., Kang, J. Q., Song, L., Dibbens, L., Mulley, J., and Macdonald, R. L. (2006) δ subunit susceptibility variants E177A and R220H associated with complex epilepsy alter channel gating and surface expression of α4β2δ GABAA receptors J. Neurosci. 26, 1499-1506
15. Ramakrishnan, L. and Hess, G. P. (2004) On the mechanism of a mutated and abnormally functioning γ-aminobutyric acid (A) receptor linked to epilepsy Biochemistry 43, 7534-7540
16. Baulac, S., Huberfeld, G., Gourfinkel-An, I., Mitropoulou, G., Beranger, A., Prudhomme, J. F., Baulac, M., Brice, A., Bruzzone, R., and LeGuern, E. (2001) First genetic evidence of GABA(A) receptor dysfunction in epilepsy: A mutation in the γ2-subunit gene Nat. Genet. 28, 46-48
17. Krivoshein, A. V. and Hess, G. P. (2006) On the mechanism of alleviation by phenobarbital of the malfunction of an epilepsy-linked GABA(A) receptor Biochemistry 45, 11632-11641
18. Storustovu, S. I. and Ebert, B. (2006) Pharmacological characterization of agonists at δ-containing GABAA receptors: Functional selectivity for extrasynaptic receptors is dependent on the absence of γ2 J. Pharmacol. Exp. Ther. 316, 1351-1359
19. Thompson, S. A., Wingrove, P. B., Connelly, L., Whiting, P. J., and Wafford, K. A. (2002) Tracazolate reveals a novel type of allosteric interaction with recombinant γ-aminobutyric acid(A) receptors Mol. Pharmacol. 61, 861-869
20. Glykys, J., Peng, Z., Chandra, D., Homanics, G. E., Houser, C. R., and Mody, I. (2007) A new naturally occurring GABA(A) receptor subunit partnership with high sensitivity to ethanol Nat. Neurosci. 10, 40-48
21. Boehm, S. L., II, Homanics, G. E., Blednov, Y. A., and Harris, R. A. (2006) δ-Subunit containing GABAA receptor knockout mice are less sensitive to the actions of 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol Eur. J. Pharmacol. 541, 158-162
22. Wohlfarth, K. M., Bianchi, M. T., and Macdonald, R. L. (2002) Enhanced neurosteroid potentiation of ternary GABA(A) receptors containing the δ subunit J. Neurosci. 22, 1541-1549
23. Zeller, A., Jurd, R., Lambert, S., Arras, M., Drexler, B., Grashoff, C., Antkowiak, B., and Rudolph, U. (2008) Inhibitory ligand-gated ion channels as substrates for general anesthetic actions Handb. Exp. Pharmacol., 31-51
24. Meldrum, B. S. and Rogawski, M. A. (2007) Molecular targets for antiepileptic drug development Neurotherapeutics 4, 18-61
25. Mohler, H. (2006) GABAA receptors in central nervous system disease: Anxiety, epilepsy, and insomnia J. Recept. Signal Transduction Res. 26, 731-740
26. Atack, J. R. (2005) The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics Expert Opin. Invest. Drugs 14, 601-618
27. Agid, Y., Buzsaki, G., Diamond, D. M., Frackowiak, R., Giedd, J., Girault, J. A., Grace, A., Lambert, J. J., Manji, H., Mayberg, H., Popoli, M., Prochiantz, A., Richter-Levin, G., Somogyi, P., Spedding, M., Svenningsson, P., and Weinberger, D. (2007) How can drug discovery for psychiatric disorders be improved? Nat. Rev. Drug Discovery 6, 189-201
28. Rudolph, U. and Mohler, H. (2006) GABA-based therapeutic approaches: GABAA receptor subtype functions Curr. Opin. Pharmacol. 6, 18-23
29. Hevers, W., Hadley, S. H., Luddens, H., and Amin, J. (2008) Ketamine, but not phencyclidine, selectively modulates cerebellar GABA(A) receptors containing α6 and δ subunits J. Neurosci. 28, 5383-5393
30. 2δ GABA(A) receptors are a target for alcohol Nat. Neurosci. 5, 721-722
31. Wallner, M., Hanchar, H. J., and Olsen, R. W. (2003) Ethanol enhances α4β3δ and α6β3δ γ-aminobutyric acid type A receptors at low concentrations known to affect humans Proc. Natl. Acad. Sci. U.S.A. 100, 15218-15223
32. Wafford, K. A., van Niel, M. B., Ma, Q. P., Horridge, E., Herd, M. B., Peden, D. R., Belelli, D., and Lambert, J. J. (2009) Novel compounds selectively enhance δ subunit containing GABA A receptors and increase tonic currents in thalamus Neuropharmacology 56, 182-189
33. Borghese, C. M. and Harris, R. A. (2007) Studies of ethanol actions on recombinant δ-containing γ-aminobutyric acid type A receptors yield contradictory results Alcohol 41, 155-162
34. Kaur, K. H., Baur, R., and Sigel, E. (2009) Unanticipated structural and functional properties of δ-subunit-containing GABAA receptors J. Biol. Chem. 284, 7889-7896
35. Mody, I., Glykys, J., and Wei, W. (2007) A new meaning for "Gin & Tonic": Tonic inhibition as the target for ethanol action in the brain Alcohol 41, 145-153
36. Udgaonkar, J. B. and Hess, G. P. (1987) Chemical kinetic measurements of a mammalian acetylcholine receptor by a fast-reaction technique Proc. Natl. Acad. Sci. U.S.A. 84, 8758-8762
37. Mabry, J. and Ganem, B. (2006) Studies on the Biginelli reaction: A mild and selective route to 3,4-dihydropyrimidin-2(1H)-ones via enamine intermediates Tetrahedron Lett. 47, 55-56
38. Boussif, O., Lezoualc'h, F., Zanta, M. A., Mergny, M. D., Scherman, D., Demeneix, B., and Behr, J. P. (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine Proc. Natl. Acad. Sci. U.S.A. 92, 7297-7301
39. Hamill, O. P., Marty, A., Neher, E., Sakmann, B., and Sigworth, F. J. (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches Pfluegers Arch. 391, 85-100
40. Hess, G. P., Udgaonkar, J. B., and Olbricht, W. L. (1987) Chemical kinetic measurements of transmembrane processes using rapid reaction techniques: Acetylcholine receptor Annu. Rev. Biophys. Biophys. Chem. 16, 507-534
41. Matsubara, N. and Hess, G. P. (1992) On the mechanism of a mammalian neuronal type nicotinic acetylcholine receptor investigated by a rapid chemical kinetic technique. Detection and characterization of a short-lived, previously unobserved, main receptor form in PC12 cells Biochemistry 31, 5477-5487
42. Haas, K. F. and Macdonald, R. L. (1999) GABAA receptor subunit γ2 and δ subtypes confer unique kinetic properties on recombinant GABAA receptor currents in mouse fibroblasts J. Physiol. 514 (Part 1) 27-45
43. Hadley, S. H. and Amin, J. (2007) Rat α6β2δ GABAA receptors exhibit two distinct and separable agonist affinities J. Physiol. 581, 1001-1018
44. Rho, J. M., Donevan, S. D., and Rogawski, M. A. (1996) Direct activation of GABAA receptors by barbiturates in cultured rat hippocampal neurons J. Physiol. 497 (Part 2) 509-522
45. Neelands, T. R., Greenfield, L. J., Jr., Zhang, J., Turner, R. S., and Macdonald, R. L. (1998) GABAA receptor pharmacology and subtype mRNA expression in human neuronal NT2-N cells J. Neurosci. 18, 4993-5007
46. Orser, B. A., McAdam, L. C., Roder, S., and MacDonald, J. F. (1998) General anaesthetics and their effects on GABA(A) receptor desensitization Toxicol. Lett. 100-101, 217-224
47. Leonardi, M. and Ustun, T. B. (2002) The global burden of epilepsy Epilepsia 43 (Suppl. 6) 21-25
48. Steinbach, J. H. and Akk, G. (2001) Modulation of GABA(A) receptor channel gating by pentobarbital J. Physiol. 537, 715-733
49. Meera, P., Olsen, R. W., Otis, T. S., and Wallner, M. (2009) Etomidate, propofol and the neurosteroid THDOC increase the GABA efficacy of recombinant α4β3δ and α4β3 GABA A receptors expressed in HEK cells Neuropharmacology 56, 155-160
50. Katz, B. and Thesleff, S. (1957) A study of the desensitization produced by acetylcholine at the motor end-plate J. Physiol. 138, 63-80
51. Cash, D. J. and Hess, G. P. (1980) Molecular mechanism of acetylcholine receptor-controlled ion translocation across cell membranes Proc. Natl. Acad. Sci. U.S.A. 77, 842-846
52. Bianchi, M. T. and Macdonald, R. L. (2003) Neurosteroids shift partial agonist activation of GABA(A) receptor channels from low- to high-efficacy gating patterns J. Neurosci. 23, 10934-10943
53. Pirker, S., Schwarzer, C., Wieselthaler, A., Sieghart, W., and Sperk, G. (2000) GABA(A) receptors: Immunocytochemical distribution of 13 subunits in the adult rat brain Neuroscience 101, 815-850
54. Yang, P., Jones, B. L., and Henderson, L. P. (2005) Role of the α subunit in the modulation of GABA(A) receptors by anabolic androgenic steroids Neuropharmacology 49, 300-316
55. Kapoor, T. M., Mayer, T. U., Coughlin, M. L., and Mitchison, T. J. (2000) Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5 J. Cell Biol. 150, 975-988
56. Maliga, Z. and Mitchison, T. J. (2006) Small-molecule and mutational analysis of allosteric Eg5 inhibition by monastrol BMC Chem. Biol. 6, 2
57. Kappe, C. O. (2000) Biologically active dihydropyrimidones of the Biginelli-type: A literature survey Eur. J. Med. Chem. 35, 1043-1052
58. Cho, H., Ueda, M., Shima, K., Mizuno, A., Hayashimatsu, M., Ohnaka, Y., Takeuchi, Y., Hamaguchi, M., Aisaka, K., and Hidaka, T. 1989, Dihydropyrimidines: Novel calcium antagonists with potent and long-lasting vasodilative and antihypertensive activity J. Med. Chem. 32, 2399-2406
59. Atwal, K. S., Rovnyak, G. C., Kimball, S. D., Floyd, D. M., Moreland, S., Swanson, B. N., Gougoutas, J. Z., Schwartz, J., Smillie, K. M., and Malley, M. F. (1990) Dihydropyrimidine calcium channel blockers. 2. 3-Substituted-4-aryl-1, 4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines J. Med. Chem. 33, 2629-2635 (Pubitemid 20274224)
60. Arias, H. R., Bhumireddy, P., and Bouzat, C. (2006) Molecular mechanisms and binding site locations for noncompetitive antagonists of nicotinic acetylcholine receptors Int. J. Biochem. Cell Biol. 38, 1254-1276
61. Dilger, J. P., Boguslavsky, R., Barann, M., Katz, T., and Vidal, A. M. (1997) Mechanisms of barbiturate inhibition of acetylcholine receptor channels J. Gen. Physiol. 109, 401-414
62. Khanetskyy, B., Dallinger, D., and Kappe, C. O. (2004) Combining Biginelli multicomponent and click chemistry: Generation of 6-(1,2,3-triazol-1- yl)-dihydropyrimidone libraries J. Comb. Chem. 6, 884-892