Robert W. Peoples, Ph.D.

Assocate Professor

Schroeder Complex 429J

(414) 288-6678

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Research Interests:

The amino acid glutamate is the predominant excitatory neurotransmitter in the mammalian brain. The N-methyl-D-aspartate (NMDA) glutamate receptor-ion channel plays essential roles in central nervous system function, participating in cognition, motor function, sensory processing, and learning. Research in my laboratory has focused on defining the molecular mechanisms and sites of action of alcohols and other CNS depressants on the NMDA receptor, which is considered to be one of the primary targets of alcohol action in the brain. This has involved investigation of the specific sites and precise molecular mechanisms by which alcohols and related agents interact with NMDA receptors. Because these sites may be located in the membrane-associated domains of these receptor-channels, this research has also involved characterizing the structure and function of these regions. Research in my laboratory has also included investigation of the structure, function, and alcohol sensitivity of purinergic receptors activated by extracellular ATP, as well as the study of novel mechanisms of intracellular regulation of receptors activated by the inhibitory amino acid glycine.

Selected Publications

1. Salous, A., Ren, H., Lamb, K.A., Hu, X.-Q., Lipsky, R.H., and Peoples, R.W.:  Differential actions of ethanol and trichloroethanol at sites in the M3 and M4 domains of the NMDA receptor NR2A subunit.  Brit. J. Pharmacol. (in press).
2. Yevenes, G.E., Moraga-Cid,G., Peoples, R.W., Schmalzing, G., and Aguayo, L.G.:  A selective Gbg-linked intracellular mechanism for modulation of a ligand-gated ion channel by ethanol.  Proc. Natl. Acad. Sci. USA 105: 20523-20528, 2008..
3. Liu, Y.-W., Luo, J.-L., Ren, H., Peoples, R.W., Ai, Y.-X., Liu, L.-J., Pang, Y.-P., Li, Z.-W.,  Han, Y.-F., and Li, C.-Y.:  Inhibition of NMDA-gated ion channels by bis(7)-tacrine: whole-cell and single-channel studies.  Neuropharmacol. 54: 1086-1094, 2008.
4. Ren, H., Salous, A.K., Paul, J.M., Lamb, K.A, .Dwyer, D.S., and Peoples, R.W.:  Functional interactions of alcohol-sensitive sites in the NMDA receptor M3 and M4 domains.  J. Biol. Chem. 283: 8250-8257, 2008.
5. Hu, X.-Q., and Peoples, R.W.:  The 5-HT3B subunit confers spontaneous channel opening and altered ligand properties of the 5-HT3 receptor.  J. Biol. Chem. 283: 6826-68231, 2008.
6. Sun, H., Hu, X., Emerit, M.B., Schoenebeck, J.C., Kimmel, C.E., Peoples, R.W., Miko, A., and Zhang, L.:  Modulation of 5-HT3 receptor distribution by the light chain of MAP1B expressed in HEK 293 cells.  J. Physiol. 586: 751-762, 2008.
7. Hu, X.-Q., and Peoples, R.W.:  Arginine 246 in the pre-transmembrane domain 1 region alters 2,2,2-trichloroethanol action in the 5-HT3A receptor.  J. Pharmacol. Exp. Ther. 324: 1011-1018, 2008.
8. Ren, H., Salous, A.K., Paul, J.M., Lipsky, R.H., and Peoples, R.W.:  Mutations at F637 in the NMDA receptor NR2A subunit M3 domain influence agonist potency, ion channel gating, and alcohol action.  Br. J. Pharmacol. 151: 749-57, 2007.
9. Lobner, D., Piana, P.M.T., Salous, A.K., Peoples, R.W.:  b-N-methylamino-l-alanine enhances neurotoxicity through multiple mechanisms.  Neurobiol. Dis. 25: 360-6, 2007.
10. Hu, X.-Q., Sun, H., Peoples, R.W., Ren, H., and Zhang, L.:  An interaction involving an arginine residue in the cytoplasmic domain of the 5-HT3A receptor contributes to receptor desensitization mechanism.  J. Biol. Chem. 281: 21781-8, 2006.
11. Xiong, K., Stewart, R.R., Hu, X.-Q., Werby, E., Peoples, R.W., Weight, F.F., Li, C.:  Role of extracellular histidines in agonist sensitivity of the rat P2X4 receptor.  Neurosci. Lett. 365: 195-9, 2004.
12. Honse, Y., Ren, H., Lipsky, R.H., and Peoples, R.W.:  Sites in the fourth membrane-associated domain regulate alcohol sensitivity of the NMDA receptor.  Neuropharmacol. 46: 647-654, 2004.
13. Akinshola, B.E., Yasuda, R.P., Peoples, R.W., and Taylor, R.E.:  Ethanol sensitivity of recombinant homomeric and heteromeric AMPA receptor subunits expressed in Xenopus oocytes.  Alcohol. Clin. Exp. Res. 27: 1876-1883, 2003.
14. Ren, H., Honse, Y., and Peoples, R.W.:  A site of alcohol action in the fourth membrane-associated domain of the n-methyl-d-aspartate receptor.  J. Biol. Chem. 278: 48815-48820, 2003.
15. Kanemitsu, Y., Hosoi, M., Zhu, P.J., Weight, F.F., Peoples, R.W., McLaughlin, J.S., and Zhang, L.:  Dynorphin A inhibits NMDA receptors through a pH dependent mechanism.  Mol. Cell. Neurosci. 24: 525-537, 2003.
16. Yevenes, G.E., Peoples, R.W., Tapia, J.C., Parodi, J., Soto, X., Olate, J., and Aguayo, L.G.:  Modulation of glycine-activated ion channel function by G protein bg subunits.  Nat. Neurosci. 6: 819-824, 2003.
17. Ren, H., Honse, Y., Karp, B.J., Lipsky, R.H., and Peoples, R.W.:  A site in the fourth membrane-associated domain of the NMDA receptor regulates desensitization and ion channel gating.  J. Biol. Chem. 278: 276-283, 2003.
18. Peoples, R.W., and Ren, H.:  Inhibition of N-methyl-d-aspartate receptors by long-chain diols: implications for the mechanism of the alcohol cutoff effect.  Mol. Pharmacol. 61: 169-176, 2002.
19. Peoples, R.W., and Stewart, R.R.:  Alcohols inhibit N-methyl-d-aspartate receptors via a site exposed to the extracellular environment.  Neuropharmacol. 39: 1681-1691, 2000.
20. Xiong, K., Peoples, R.W., Montgomery, J., Chiang, Y., Stewart, R.R., Weight, F.F., and Li, C.:  Differential modulation by copper and zinc of P2X2 and P2X4 receptor function.  J. Neurophysiol. 81: 2088-2094, 1999.
21. Li, C., Peoples, R.W., Lanthorn, T.H., Li, Z., and Weight, F.F.:  Distinct ATP-activated currents in different types of rat dorsal root ganglion neurons.  Neurosci. Lett. 263: 57-60, 1999.
22. Peoples, R.W., and Weight, F.F.:  Differential alcohol modulation of GABAA and NMDA receptors.  NeuroReport 10: 97-101, 1999.
23. Peoples, R.W., and Weight, F.F.:  Inhibition of excitatory amino acid-activated currents by trichloroethanol and trifluoroethanol.  Br. J. Pharmacol. 124: 1159-1164, 1998.
24. Peoples, R.W., and Li, C.: Inhibition of NMDA-gated ion channels by the P2 purinoceptor antagonists suramin and reactive blue 2.  Br. J. Pharmacol. 124: 400-408, 1998.
25. Zhai, J., Peoples, R.W., and Li, C.:  Proton inhibition of GABA-activated current in rat primary sensory neurons.  Pflügers Arch. 435: 539-544, 1998.
26. Li, C., Peoples, R.W., and Weight, F.F.:  Ethanol-induced inhibition of a neuronal P2X purinoceptor by an allosteric mechanism.  Br. J. Pharmacol. 123: 1-3, 1998.