Laboratory for Integrative Neuroscience
NIAAA/NIH
5625 Fishers Lane, Room 4N07
Bethesda, MD 20892-9411
Tel: 301-443-3755
Fax: 301-480-0466
Email: lzhang@mail.nih.gov

Research Interest

5-HT₃ and glycine receptors are members of the Cys-loop superfamily of ligand-gated ion channels. These receptors are the primary targets for alcohol and other drugs of abuse in the brain. While the high-affinity competitive antagonists of 5-HT₃ receptors have been wildly used for the treatment of emesis and irritable bowel syndrome, the research looking for widespread application for 5-HT₃ receptor antagonist is far from over. On the other hand, glycine receptors are shown to play an important role in neuromotor coordination and antinociception. However, the therapeutic agents targeted on glycine receptors have not been developed. Future development largely depends on 1) exploration of the roles of 5-HT₃ receptors and glycine receptors in central and peripheral nervous system; 2) exploration of the molecular pathways and agents (endogenous/exogenous modulators) that regulate 5-HT₃ and glycine receptor distribution, trafficking and function under various physiological and pathological processes. We combine a variety of molecular biological, biochemical and electrophysiological techniques to address these questions.

Selected Publications

Xiong, W., Hosoi M., Koo, B.N. and Zhang, L. Anandamide inhibition of 5-HT_3A receptors varies with receptor desensitization and density. Mol. Pharmacol. 73:314-322, 2008.

Sun, H., Hu, X-Q., Schoenebeck, J. Peoples, R.W., Ren, H., William, C.K. Emerit M. and Zhang, L. Modulation of 5-HT_3A receptor desensitization kinetics by MAP1B expressed in HEK 293 cells. The Journal of Physiology (London) 586:751-762, 2008.

Singal S., Zhang, L., Morales, M. and Oz M. Antisychotic clozapine inhibits the function of a7 nicotinic acetylcholine receptors. Neuropharmacology, 52:387-94, 2007.

Hu, X.Q., Sun, H., Ren, H., Peoples, RW and Zhang, L. An interaction involving an argining in the cytoplasmic domain of 5-HT_3A receptor contributes to receptor desensitization mechanism. J. Biol. Chem. 281:21781-21788, 2006.

Hejazi, N., Zhou, c., Oz, m., Ye, JH and L. Zhang: Δ⁹-Tetrahydracannabinol and Endogenous Cannabinoid Anandamide Directly Potentiate the Function of Glycine Receptors Mol. Pharmcol. 69:991-997, 2006.

Oz, M., Jackson, S.N., Woods, A.S., M. Morales, M and Zhang, L. Additive effects of endogenous cannabinoid anandamide and ethanol on a7-nicotinic acetylcholine receptor-mediated responses in Xenopus oocytes The J. Pharm. Exp. Ther. 313:1272-1280, 2005.

Oz, M., Zhang, L. Rotondo, A., Sun, H. and Morales, M. Differential effects of endogenous and synthetic cannabinoids on a 7 nicotinic acetylcholine receptor-mediated responses in Xenopus oocytes The J. Pharm. Exp. Ther. 310:1152-1160, 2004.

Miko, A., Werby, E., Sun, H., Healey, J. and Zhang, L. A TM2 residue determines the spontaneous opening of homomeric and heteromeric GABA-gated ion channels. J. Biol. Chem 279:22833-22840, 2004.

Hu, X-Q, Zhang, L., Stewart R.R. and Weight, F.F. Arginine 222 in the pre-transmembrane domain 1of 5-HT_3A receptors links agonist binding to channel gating J. Biol. Chem 278:46583-46589, 2003.

Kanemitsu, Y., Hosoi, M., Zhu, P-J., Weight, F. F., Peoples, W. R. Mclaughlin, J.S. and Zhang, L. Dynorphin A inhibits NMDA receptors through a pH dependent mechanism. Mol. Cellular Neurosci. 24:525-537, 2003.

Sun, H., Hu, X. Q., Moradel, E., Weight, F.F. and Zhang, L. Modulation of 5-HT₃ receptor-mediated responses and trafficking by activation of protein kinase C. J. Biol. Chem. 278:34150-34157, 2003.

Oz, M., Zhang, L. and Morales, M. Endogenous cannabinoid, anandamide acts as a noncompetitive inhibitor on 5-HT₃ receptor-mediated responses in Xenopus oocytes. Synapse 46:150-156, 2002.

Zhang, L., Hosoi, M., Fukuzawa, Sun, H., M., Rawlings R. R. and Weight, F.F. Distinct molecular basis for differential sensitivity of the 5-HT_3A receptor to ethanol in the absence and presence of agonist. J. Biol. Chem. 277:46256-46264, 2002.


Book Chapters

1. Thompson AJ, Zhang L. and Lummis, SCR. 5-HT₃ Receptor. In Ruth RL eds. The Serotonin Receptors: From Molecular Pharmacology to Therapeutics. The Humana Press, 439-457, 2006

2. Zhang L. and SCR Lummis. 5-HT₃ Receptors. In Bowery N. eds. Allosteric Receptors Modulation in Drug Targeting. Marcel Dekker, 2006