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Esam E. El-Fakahany, Ph.D. Professor, Division of Neuroscience Research, Department of Psychiatry E-mail: elfak001@umn.edu

Research Interests:

This laboratory combines expertise in signal transduction and molecular biology. One of the main research areas is the molecular mechanisms of coupling of neuronal muscarinic cholinergic receptors to second messenger signaling systems. Particular interests include: the interplay among phosphoinositide hydrolysis, increased intracellular calcium activation of protein kinases, and the generation of nitric oxide; the feedback regulation of receptor sensitivity by these various second messengers; and the effects of psychotropic drugs on second messenger signals in the brain.

The laboratory also investigates the regulation of messenger RNA encoding the muscarinic receptor by different pharmacological treatments, aging, or Alzheimer's disease. Current efforts aim at studying the specific role of certain amino acid residues in the muscarinic receptor protein in receptor function and regulation. The molecular mechanisms of neurotoxicity of the ß-amyloid protein that accumulates in senile plaques of Alzheimer's brains in relation to nitric oxide generation is also under investigation.

Selected Publications:

De Lorme KC, Grant MK, Noetzel MJ, Polson SB, El-Fakahany EE. Long-term changes in the muscarinic M1 receptor induced by instantaneous formation of wash-resistant xanomeline-receptor complex. J Pharmacol Exp Ther. 2007 Dec;323(3):868-76.

Kane BE, Grant MK, El-Fakahany EE, Ferguson DM. Synthesis and evaluation of xanomeline analogs-Probing the wash-resistant phenomenon at the M(1) muscarinic acetylcholine receptor. Bioorg Med Chem. 2007 Oct 22.

Machová E, Jakubík J, El-Fakahany EE, Dolezal V. Wash-resistantly bound xanomeline inhibits acetylcholine release by persistent activation of presynaptic M(2) and M(4) muscarinic receptors in rat brain. J Pharmacol Exp Ther. 2007 Jul;322(1):316-23.

Michal P, El-Fakahany EE, Dolezal V. Muscarinic m2 receptors directly activate gq/11 and gs g-proteins. J Pharmacol Exp Ther. 2007 Feb;320(2):607-14.

De Lorme KC, Sikorski KL, Grant MK, El-Fakahany EE. Long-term wash-resistant effects of brief interaction of xanomeline at the M1 muscarinic receptor. Neurosci Lett. 2006 Dec 13;410(1):11-4.

Jakubik J, El-Fakahany EE, Dolezal V. Differences in kinetics of xanomeline binding and selectivity of activation of G proteins at M(1) and M(2) muscarinic acetylcholine receptors. Mol Pharmacol. 2006 Aug;70(2):656-66.

Current Graduate Students:

Meredith Noetzel (Neuroscience, University of Minnesota).

Recent Graduate Students

Vickram Ramkumar (Ph.D., Pharmacology; Regulation of neuronal calcium channels). Assistant Professor of Pharmacology, University of Southern Illinois Medical School.

Norman Lee (Ph.D., Pharmacology, Modulation of muscarinic acetylcholine receptors.). Laboratory Director, Institute of Genomic Research, Gaithersburg, MD.