Abstracts - Speakers

First Annual Waggoner Center Advance - March 22, 2013

Garrett Cornelison, BS

Graduate Student, Mihic Lab

Identification of Heptapeptide Modulators of the Glycine Receptor via Phage Display

Unlike many prescribed medications, as well as other common drugs of abuse, ethanol acts on a wide variety of targets in the CNS, including various enzymes, neurotransmitter receptors and ion channels. This large number of putative ethanol targets in the brain has made it difficult for researchers to determine which of these targets are responsible for mediating the various behavioral effects of ethanol. In order to shed light on this important area of research we are attempting to develop tools that will allow us to look at each of these targets individually. Previous work demonstrated the feasibility of using a phage display screening procedure to identify specific peptide modulators of various ion channel targets of ethanol. Our goal is to identify highly potent peptides capable of inhibiting or mimicking the effects of ethanol at specific targets. These peptides can then be utilized in animal studies to identify the roles of specific ethanol targets in intoxication and behavioral dependence. Using phage display we identified multiple heptapeptide sequences that were then used to synthesize peptides to test as modulators of the glycine receptor, a putative target of ethanol in vivo. These peptides variably enhanced the effects of glycine on glycine receptors as determined via two-electrode voltage clamp electrophysiology in the Xenopus oocyte heterologous expression system.