Frederick J. Ehlert, Ph.D.

Professor of Pharmacology

A.B., 1974, Biology, California State University, Humboldt
Ph.D., 1978, Pharmacology, University of California, Irvine
Research Career Development Award, NIH
Syntex Award in Receptor Research

Summary of Research: Our research focuses on how drugs turn on receptors to trigger cellular responses. We approach this topic from two opposite directions, depending on the receptor of interest. In some instances, we identify the intracellular signaling mechanism of a receptor and study how this mechanism is translated into cellular responses. In other instances, we work backwards to discover the physiological function and signaling mechanism of a receptor whose presence in a tissue is known, but whose function is unknown. An example of the latter approach is our work on the M2 muscarinic receptor in smooth muscle. We showed that the M2 receptor functions to tune up the contractile action of the M3 receptor and to inhibit the relaxant action of ß-adrenoceptors in the gastrointestinal tract and urinary bladder.
In the course of our work we have developed novel methods to identify a receptor mediating a functional response using drugs that turn on and turn off receptors. Specifically we have developed methods 1) to analyze responses that are mediated by more than one receptor, 2) to analyze the behavior of drugs that act allosterically to tune up or tune down the actions of another drug, and 3) to determine whether the G protein with which a receptor interacts influences how a drug turns on the receptor. To explore receptor function further we use mutant mice lacking muscarinic receptor subtypes and we synthesize novel, covalently acting drugs to block muscarinic receptor subtypes selectively.