** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** ANNUAL ECONOMIC LOSS FOR THE UNITED STATESBEEF INDUSTRY DUE TO TALL FESCUE TOXICOSIS WAS ESTIMATED TO BE $2 BILLION, OF WHICH $500 MILLION WAS DUE TO DECREASED GROWTH OF CALVES CONSUMING TALL FESCUE CONTAINING ERGOT ALKALOIDS. ERGOT ALKALOIDS INDUCE VASOCONSTRICTION OF CORE AND PERIPHERAL BLOOD VESSELS. THE OVERALL GOAL OF THIS PROJECT IS TO ELUCIDATE THE MOLECULAR MECHANISMS BY WHICH SEROTONIN MITIGATES ERGOT ALKALOID-INDUCED VASOCONSTRICTION IN BEEF CATTLE. THE OBJECTIVES OF THIS PROJECT ARE TO DETERMINE: 1) IF SEROTONIN CAN RELAX ERGOT ALKALOID-CONSTRICTED BLOOD VESSELS, 2) WHICH SEROTONIN RECEPTOR ACTIVATES VASORELAXATION, AND 3)WHICH DOWNSTREAM PROTEINS MEDIATE THE RELAXATION RESPONSE. IT IS ANTICIPATED THAT THIS PROJECT WILL LEAD TO THE FIRST REPORT DEMONSTRATING THAT: SEROTONIN CAN RELAX ERGOT ALKALOID-CONSTRICTED BLOOD VESSELS, SEROTONIN RECEPTOR 5-HT4ACTIVATES THE RELAXATION RESPONSE, AND THAT DOWNSTREAM PROTEINS (CALCIUMCHANNELS, POTASSIUM CHANNELS, MYOSIN LIGHT CHAIN PHOSPHATASE, AND HEAT SHOCK PROTEINS) MEDIATE THE RELAXATION RESPONSE. THIS NEW KNOWLEDGE WILL AID IN EFFORTS TO DEVELOP STRATEGIES TO AMELIORATE VASOCONSTRICTION THAT OCCURS DURING FESCUE TOXICOSIS IN BEEF CATTLE.