muscarinic receptors, drug receptor interactions, antagonists, receptor subtypes, signaling pathways
1989-1994, Research Career Development Award from NIH
1995, Syntex Award in Receptor Research
Dr. Ehlert investigates the function of muscarinic receptor subtypes in brain and peripheral tissues. In addition, Dr. Ehlert specializes in the analysis of drug-receptor interactions and in the development of novel subtype-selective irreversible antagonists.
The molecular mechanisms of numerous physiological processes have recently been explained through advances in molecular biology and cellular signaling. However, in some instances, receptor subtypes and signaling pathways have been detected whose roles in physiology are unknown. The goal of our research can be formulated as the general question, “what is the physiological role of a particular gene product or signaling pathway?" One specific aim is to identify the functional roles of M2 muscarinic receptors in smooth muscle. A variety of techniques including cell culture, second messenger assays, and contractile measurements on isolated smooth muscle from wild type animals and muscarinic receptor knockout mice are used to investigate the contractile role of M2 receptors in smooth muscle. Another area of research is the analysis of models for drug-receptor interactions and how pharmacological techniques can be used to identify the functional role of interacting receptors in a variety of physiological responses.
Matusi, M., Griffin, M.T., Shehnaz, D. Taketo, M.M. and Ehlert, F.J. Increased relaxant action of forskolin and isoproternol against muscarinic agonist-induced contraction in smooth muscle from M2 receptor knockout mice, J. Pharmacol. Exp. Ther. 305:106-113, 2003.
Ehlert, F.J. Pharmacological analysis of the contractile role of M2 and M3 muscarinic receptor in smooth muscle, Receptors and Channels 9:261-277, 2003.
Griffin, M.T. Hsu, J. C-H., Shehnaz, D. and Ehlert, F.J., Comparison of pharmacological antagonism of M2 and M3 muscarinic receptors expressed in isolation and in combination, Biochem. Pharmacol. 65:1227-1241, 2003.
Ehlert, F.J., N-substituted quinuclidinol esters as potential therapeutic antimuscarinic agents, Expert Opin. Ther: Patents 13:377-380, 2003.
Ehlert, F.J., Contractile role of M2 and M3 muscarinic receptors in gastrointestinal, airway and urinary bladder smooth muscle, Life Sciences 74:355-366, 2003.
Griffin, M.T., Matsui, M., Shehnaz, D., Ansari, K.Z., Taketo, M.M., Manabe T. and Ehlert, F.J., Muscarinic agonist-mediated heterologous desensitization in isolated ileum requires activation of both muscarinic M2 and M3 receptors, J. Pharmacol. Exp. Ther. 308:339-349, 2004.
Matsui, M., Yamada, S., Oki, T., Manabe, T., Taketo, M.M. and Ehlert, F.J., Functional analysis of muscarinic acetylcholine receptors using knockout mice, Life Sci. 75:2971-2981, 2004.
Ehlert, F.J, Hsu, J.C-H, Leung, K., Lee, A.G., Shehnaz, D. and Griffin, M.T., Comparison of the Antimuscarinic Action of p-fluorohexahydrosiladifenidol in ileal and tracheal smooth muscle, J. Pharmacol. Exp. Ther. 312: 592-600, 2005.
Ehlert, F.J., Griffin, M.T., Abe, D.M., Vo, T.H., Taketo, M.M., Manabe, T. and Matsui, M., The M2 muscarinic receptor mediates contraction through indirect mechanisms in mouse urinary bladder, J. Pharmacol. Exp. Ther. 313:368-378, 2005.
Ehlert, F.J., Drugs affecting the parasympathetic nervous system, in Brody’s Human Pharmacology: Molecular to Clinical, Fourth Edition, (eds. Minneman, K.M. and Wecker, L.) Mosby, St. Louis, pp 101-118, 2005.
Ehlert, F.J., Receptor Physiology, in Textbook of Critical Care, 5th Edition, M. Fink, E Abraham, J-L Vincent and P. Kochanek (Eds), Elsevier Science, Philadelphia, pp. 209-218, 2005.
Ehlert, F.J., Analysis of allosterism in functional assays, J. Pharmacol. and Exp. Ther. 315:1-15, 2005.
Sawyer, G.W., Ehlert, F.J., and Hart, J.P., Determination of the rate of muscarinic M1 receptor plasma membrane delivery using a regulated secretion/aggregation system, J. Pharmacol. Toxicol. Methods. 53:219-233, 2006.
Tran, J.A., Matsui, M. and Ehlert, F.J., Differential coupling of muscarinic M1, M2, and M3 receptors to phosphoinositide hydrolysis in urinary bladder and longitudinal muscle of the ileum of the mouse, J. Pharmacol. Exp. Ther. 2006 318: 649-656, 2006.
Griffin, M.T., Figueroa, K.W., Liller, L. and Ehlert, F.J., Estimation of agonist activity at G protein coupled receptors: Analysis of M2 muscarinic receptor signaling through Gi/o, Gs and G15, J. Pharmacol. Exp. Ther. 321: 1193-1207 2007.
Ehlert, F.J., Ahn, S., Pak, K.J., Park, G.J., Sangnil, M.S., Tran, J.A. and Matsui, M., Neuronally released acetylcholine acts on the M2 muscarinic receptor to oppose the relaxant effect of isoproterenol on cholinergic contractions in mouse urinary bladder, J. Pharmacol. Exp. Ther. 322: 631-637, 2007.
Sawyer, G.W., Ehlert, F.J. and Shults, C.A., Cysteine Pairs in the third intracellular loop of the muscarinic M1 acetylcholine receptor play a role in agonist-induced internalization, J. Pharmacol. Exp. Ther. 324: 196-205, 2008.
Ehlert, F.J. and Griffin, M.T. Two-state Models and the Analysis of the allosteric effect of gallamine at the M2 muscarinic Receptor, J. Pharmacol. Exp. Ther. 325:1039-1060, 2008.
Ehlert, F.J., On the analysis of ligand-directed signaling at G protein-coupled receptors, Naunyn-Schmiedeberg's Arch. Pharmacol. 377:549-577, 2008.
Suga, H., Figueroa, K.W. and Ehlert, F.J., Use of acetylcholine mustard to study allosteric interactions at the M2 muscarinic receptor, J. Pharmacol. Exp. Ther. 327:518 – 528, 2008.
Figueroa, K.W., Griffin, M.T. and Ehlert, F.J., Selectivity of Agonists for the Active State of M1 – M4 Muscarinic Receptor Subtypes, J. Pharmacol. Exp. Ther. 328:331-341, 2009.
Tran, J.A., Chang, A., Matsui, M. and Ehlert, F.J., Estimation of relative microscopic affinity constants of agonists for the active state of the receptor in functional studies on M2 and M3 muscarinic receptors, Mol. Pharmacol. 75:381-396, 2009.
American Society for Pharmacology & Experimental Therapeutics
Society for Neuroscience
Interdepartmental Neuroscience Program
Medicinal Chemistry and Pharmacology