Mitigation of Sustained Ergot Alkaloid-Induced Vasoconstriction in Beef Cattle by Serotonin

This project is an application for Dr. Ronald Trotta to complete an AFRI Postdoctoral Fellowship (A7201) under the mentorship of Dr. David Harmon at the University of Kentucky. The overall goal of this research project is to elucidate the molecular mechanisms by which serotonin mitigates ergot alkaloid-induced vasoconstriction in beef cattle. The objectives of the project plan are to determine: 1) if serotonin can relax bovine blood vessels that are pre-contracted with ergot alkaloids, 2) the primary receptor mediating vasorelaxation responses to serotonin, 3) downstream proteins involved with serotonin receptor-mediated vasorelaxation of blood vessels pre-contracted with ergot alkaloids. The applicant will also complete several programs outlined in the Training/Career Development Plan to gain and enhance professional skills focused on teaching, leadership, team management, and research administration. This project addresses AFRI Farm Bill Priority Animal Health and Production and Animal Products: Animal Nutrition, Growth and Lactation (A1231) by describing molecular mechanisms associated with the onset and amelioration of fescue toxicosis, a $2 billion issue that decreases the weaning weight of 9 million U.S. beef calves by 50 lbs per animal on average annually. It is anticipated that this project will lead to the first report demonstrating that: serotonin can induce vasorelaxation of ergot alkaloid-constricted bovine blood vessels through 5-HT4 activation which mediates signaling to multiple downstream proteins (calcium channels, potassium channels, myosin light chain phosphatase, small heat shock proteins) resulting in vasorelaxation. Outputs generated will offer long-term solutions to increase productivity, sustainability, and economic competitiveness of the U.S. beef industry.