After completing undergraduate work in Psychology at Montana State University, Keith Parker received a Ph.D. in Pharmacology and Toxicology from the University of California, San Francisco in 1977. Following postdoctoral positions at the University of Colorado Health Sciences Center in Denver and the University of Denver, he moved to Western Montana College in 1981 where he remained until 1993. At that time he assumed his current position at the University of Montana.

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INTERESTS OF THE PARKER LABORATORY

Our group has a long-standing applied interest in better understanding headache, and particularly in developing better anti-migraine headache drugs. For many years the neurotransmitter serotonin (5HT) has been implicated in the pathology of migraine headache. For this reason, we have focused our work on the receptors that bind to serotonin, thereby transferring a signal to the interior of nerve and other cells. Because serotonin mechanisms are also associated with other biomedical problems such as depression, anxiety, obsessive-compulsive disorders, and panic disorder, our work with 5HT receptors has additional potential applications.

Much of the work in the Parker laboratory is focused on the interface between a particular serotonin receptor, the 5HT1a receptor, and a special type of intracellular signal transducing molecule known as a G protein. Most of the serotonin receptors belong to a large family of receptors that are coupled to G proteins. Thus, the 5HT1a receptor is not only related to other serotonin receptors, but to a variety of neurotransmitter receptors such as the beta adrenergic and dopamine receptors. Because of these multiple relationships, the 5HT1a receptor is a model receptor, and information gained from studying it potentially has implications for other types of receptor systems.

We work predominantly with the human 5HT1a receptor, which has been cloned and expressed in a cell culture system. Since the entire amino acid sequence of this receptor is known, we can utilize that information to synthesize portions of the receptor for experimental tools. The G protein coupled receptors also show a characteristic structural pattern in which the receptor protein snakes through the membrane seven times, then loops outside and inside the cell a number of times connecting the membrane segments. The intracellular loops are thought to couple receptor to G protein; thus, our recent work has emphasized small peptides, which we have synthesized based upon the sequences of intracellular loops 2 and 3. We are using these peptides as molecular tools for analyzing the specific structural requirements of the receptor-G protein system. Additionally, the peptides may eventually be prototypes for new drug structures.

As a secondary focus of the laboratory, we analyze the potential of natural product drugs for anti-migraine treatments. Using the same cultured serotonin receptors available for our other studies, we examine the ability of natural product drugs to alter binding of known drugs to the receptors. The natural products are derived from plants used by native cultures throughout the world to treat headache. This area of study, known as ethnopharmacology, provides initial clues for investigations of new drugs, previously un-examined by scientific experimentation.

Some of the specific questions we are trying to answer include:

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SELECTED PUBLICATIONS

Thiagaraj, H.V., Thompson, C.M., Russo, E.B., Burnett, A., Goldstein, E., and Parker, K.K. “Binding Properties of Dipropyltryptamine at the Human 5HT1a Receptors.“Pharmacology 74: 193-199, 2005.

Smith, J.R., Thiagaraj, H.V., Seaver, B., and Parker, K.K. “Differential Activity of Lipoic Acid Enantiomers in Cell Culture.” J. Herbal Pharmacoth. 5 (3): 43-54, 2005.

Russo, E.B., Burnett, A., Hall, B., and Parker, K.K. "Agonistic Properties of Cannabidiol at 5-HT1A Receptors." Neurochemical Res. 30 (8): 1037-1043, 2005.

Thiagaraj, H.V., Ortiz, T.C., Devereaux, M.C. Jr., Seaver, B., Hall, B., and Parker, K.K. “Regulation of G Proteins by Human 5-HT1a Receptor TM3/i2 and TM5/i3 Loop Peptides.” Neurochemistry International, 50: 109-118, 2007.