Influence of Prolonged Serotonin and Ergovaline Pre-Exposure on Vasoconstriction Ex Vivo

Abstract

Ergot alkaloid mycotoxins interfere in many functions associated with serotonergic neurotransmitters. Therefore, the objective was to evaluate whether the association of serotonin (5-hydroxytryptamine, 5-HT) and ergot alkaloids during a 24 h pre-incubation could affect the vascular contractile response to ergot alkaloids. To evaluate the effects of 24 h exposure to 5-HT and ergot alkaloids (ergovaline, ERV), two assays were conducted. The first assay determined the half-maximal inhibitory concentration (IC50) following the 24 h pre-exposure period, while the second assay evaluated the effect of IC50 concentrations of 5-HT and ERV either individually or in combination. There was an interaction between previous exposure to 5-HT and ERV. Previous exposure to 5-HT at the IC50 concentration of 7.57 × 10−7 M reduced the contractile response by more than 50% of control, while the exposure to ERV at IC50 dose of 1.57 × 10−10 M tended to decrease (p = 0.081) vessel contractility with a response higher than 50% of control. The 24 h previous exposure to both 5-HT and ERV did not potentiate the inhibitory response of blood vessels in comparison with incubation with each compound alone. These results suggest receptor competition between 5-HT and ERV. More studies are necessary to determine the potential of 5-HT to treat toxicosis caused by ergot alkaloids.

Serotonin receptor‐mediated vasorelaxation occurs primarily through 5‐HT4 activation in bovine lateral saphenous vein

“…In the current study, increased concentrations of 5‐HT induced a contractile response greater than the pre‐contracted saphenous vein. This is similar to prior studies in cattle saphenous vein that evaluated 5‐HT without a pre‐contraction period (Klotz et al., 2012 , 2013 ; Valente et al., 2021 ). Notably, the 5‐HT concentration curve of the bovine lateral saphenous vein of the current study appears to be similar to the response observed by Watts (Watts, 2016 ) in the pre‐contracted rat tail artery in the presence of 5‐HT 2A and 5‐HT 1B antagonists.…”

“…Dietary consumption of ergot alkaloids in toxic endophyte‐infected tall fescue has been shown to decrease vascular contractile responses to individual ergopeptine alkaloids, 5‐HT, and agonists selective for the 5‐HT 2A receptor in isolated bovine lateral saphenous veins and mesenteric blood vessels (Egert et al., 2014 ; Klotz et al., 2010 , 2012 , 2013 , 2016 , 2018 ). Additionally, increasing exposure of the isolated bovine lateral saphenous vein to ergovaline in vitro results in increased tissue concentrations of ergovaline, suggesting bioaccumulation of ergot alkaloids occurs in vascular tissue (Klotz et al., 2009 ; Valente et al., 2021 ). Ergot alkaloids can act as both agonists and antagonists of 5‐HT 2A ‐mediated vasoconstriction (Klotz et al., 2016 , 2018 ; Trotta et al., 2018 ), depending on the dose and duration of ergot alkaloid exposure (Trotta et al., 2023 ).…”

Sustained vascular contractile response induced by an R- and S-epimer of the ergot alkaloid ergocristine and attenuation by a noncompetitive antagonist

“…Ergot alkaloids bind nonspecifically to vascular receptors ( Saper and Silberstein, 2006 ) such as the serotonin receptor, mediating peripheral vascular contracture ( Valente et al, 2022 ). However, POB is foremost an alpha-adrenergic antagonist ( Yoham, 2022 ); therefore, the present study supports the involvement of alpha-adrenergic receptors mediating arterial contraction after exposure to R- or S -epimers of ergot alkaloids.…”

Global Impact of Ergot Alkaloids

“…A very specific pathology associated with ergot alkaloids and ergotism is a chronic vasoconstriction. Yonpaim et al [ 21 ] looked at the acute exposure of ergot alkaloids on vasoactivity in ovine vasculature, and Valente et al [ 22 ] evaluated prolonged ergot alkaloid exposure on the vasoactivity of bovine vasculature. Both studies [ 21 , 22 ] respectively evaluated aspects related to the ability of ergot alkaloids to interact with adrenergic and serotonergic receptors [ 23 ], and both papers concluded that receptor-mediated treatments for ergot alkaloid-induced vasoconstriction could be explored as potential therapies.…”

“…Yonpaim et al [ 21 ] looked at the acute exposure of ergot alkaloids on vasoactivity in ovine vasculature, and Valente et al [ 22 ] evaluated prolonged ergot alkaloid exposure on the vasoactivity of bovine vasculature. Both studies [ 21 , 22 ] respectively evaluated aspects related to the ability of ergot alkaloids to interact with adrenergic and serotonergic receptors [ 23 ], and both papers concluded that receptor-mediated treatments for ergot alkaloid-induced vasoconstriction could be explored as potential therapies. From a systemic evaluation of ergot alkaloids’ impact on the whole animal or microbiome, to the study of a specific symptom, there is much yet to be learned about how ergot alkaloids disrupt mammalian physiology.…”