Association of serotonin and ergot alkaloids on tissue partitioning and contractile response of bovine blood vessels

Authors: VALENTE, ERITON - Western Paraná State University; HARMON, DAVID - University Of Kentucky; MAY, JOHN - University Of Kentucky; JI, HUIHUA - University Of Kentucky; TROTTA, RONALD - University Of Kentucky; Klotz, James

Submitted to: Current Research in Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/26/2025
Publication Date: 10/3/2025
Citation: Valente, E.E., Harmon, D.L., May, J., Ji, H., Trotta, R.J., Klotz, J.L. 2025. Association of serotonin and ergot alkaloids on tissue partitioning and contractile response of bovine blood vessels. Current Research in Toxicology. 10. Article 100272. https://doi.org/10.1016/j.crtox.2025.100272.
DOI: https://doi.org/10.1016/j.crtox.2025.100272

Interpretive Summary: Tall fescue grass makes up a major portion of forage available to grazing livestock in the southeastern United States. It owes a lot of its success to a symbiotic relationship with a fungus. While the fungus benefits the plant, it produces ergot alkaloids which are toxins produced to minimize overgrazing. These toxins can interact with receptors in the animals body that normally interact with serotonin. This disrupts the numerous biological processes associated with serotonin such as maintenance of vascular tone and cause a syndrome collectively referred to as fescue toxicosis. This study sought to study the relationship between serotonin and the predominant ergot alkaloid in tall fescue, ergovaline by using a bovine lateral saphenous vein bioassay to assess vascular reactivity. The association and dissociation of ergovaline from serotonin receptors is much slower than that of serotonin, so it was hypothesized that an increased presence of serotonin would interfere with ergovaline binding. Blood vessels were incubated overnight with a range of concentrations of ergovaline and serotonin alone and in combination. The blood vessels were then assessed for the ability to react to increasing concentration of serotonin as well as the amount of ergovaline and serotonin that had accumulated in the tissue. The presence of serotonin did not change the negative effect that ergovaline had on the blood vessel. Also tissue accumulation of ergovaline reduced tissue serotonin as well as vascular contractility. This work will be primarily of interest to other researchers looking to better understand the relationship of serotonin and ergot alkaloids in grazing livestock as a potential avenue to alleviate this malady.

Technical Abstract: Ergot alkaloids can bind with serotonin receptors interfering with many physiological functions. However, the mechanism by which ergot alkaloids cause persistent effects after cessation of exposure has not been established. The objective was to evaluate whether the association of 5-HT and ergot alkaloids ergovaline in a 24-h pre-incubation can affect vascular tissue accumulation, relaxation and contractile response. Cross-sections of the cranial branch of lateral saphenous veins were collected from five Bos taurus steers were used to evaluate tissue accumulation and contractility. For tissue accumulation the treatments were organized in a factorial arrangement 3 x 4, where three levels of ergovaline (2.01x10-8 M, 2.01x10-7 M and 2.01x10-6 M) were combined with four levels of 5-HT (0 M, 5x10-8 M, 5x10-7 M and 5x10-6M) for incubation. After 24-h exposure to the treatments, the blood vessels were washed by changing buffer (5 mL) every 15 min for 90 min. Afterward, tissue was analyzed for ergovaline and serotonin. Contractility of a parallel set of blood vessels were evaluated in myograph after 24-h pre-incubation to the treatments: 1) no additional compound (Control); 2) tall fescue seed extract (2.01 x 10-7 M of ergovaline; ERV); 3) serotonin (5 x 10-7 M; 5HT); or 4) ERV plus 5-HT (ERV+5HT). The tissue ergovaline increased (P < 0.001) about 27.5-fold during incubation when the concentration in media was increased 100-fold. However, the presence of 5-HT did not affect (P = 0.368) tissue ergovaline accumulation. When 5-HT was not added, the addition of 2.01x10-7 and 2.01x10-6 M ergovaline reduced (P < 0.05) the 5-HT concentration in the blood vessel. Pre-incubation with ergovaline reduced contractile response by about 95% (P < 0.05) and pre-incubation with both 5-HT and ergovaline did not change the effect of ergovaline on blood vessel contractility. The tissue accumulation of ergot alkaloid reduces tissue 5-HT and blood vessel contractility.