Degree Type

Creative Component

Semester of Graduation

Fall 2018

Department

Biomedical Sciences

First Major Professor

Alan Robterson

Degree(s)

Master of Science (MS)

Major(s)

Biomedical Sciences

Abstract

Parasitic nematode infections affect millions of people worldwide and are a significant cause of human and veterinary disease. Chronic infections cause debilitating health problems in humans, domestic animals, and livestock. Infections are treated using anthelmintic drugs, some target nicotinic acetylcholine receptors located in several different tissues. The exact mode of action of antinematode drugs is unknown. Research leading to better understand the mode of action is desirable to appreciate how resistance mechanisms develop. There is an urgent need for novel therapeutic agents to overcome resistance.

This study considered Anycylstoma caninum ACR-16 as a drug target and was investigated using two-electrode voltage-clamp electrophysiology. This technique allowed us to explore several agonist and antagonists of ACR-16 and their pharmacology expressed in X. laevis oocytes. The sequence of Acn-ACR-16 was compared with Asu-ACR-16, another homomeric nicotinic acetylcholine receptor, but widely distributed in Ascaris tissue. Also, the concentration-current-response relationships and the potencies of agonists are demonstrated for Acn-ACR-16. We concluded that Acn-ACR-16 was not sensitive to many of the currently used cholinomimetic anthelmintics. Though, the A. caninum channel was most sensitive to 3-bromocytisine unlike nicotine which was the most potent agonist for A. suum ACR-16 receptor. When considering antagonist pharmacology, the A. caninum receptor was moderately inhibited by α-BTX while Asu-ACR-16 was almost insensitive.

Copyright Owner

Nicole Musselman

File Format

application/pdf

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