PSV-14 Ergovaline acts as both an agonist and antagonist on serotonin receptor 5-HT2A in bovine ruminal and mesenteric vasculature.

Abstract

Ergot alkaloids from endophyte-infected (Epichloë coenophiala) tall fescue (Lolium arundinaceum) induce vasoconstriction. Previous work has shown that serotonin receptor subtype, 5HT2A, is present in bovine ruminal (R) and mesenteric (M) vasculature, plays a role in vasoconstriction, and could be influenced by ergot alkaloids. To determine the influence of ergot alkaloids on 5HT2A, the vasoactivity of an agonist selective for 5HT2A (TCB2) was evaluated using bovine ruminal and mesenteric arteries and veins (RA, RV, MA, MV) that were exposed to ergovaline (ERV) either prior to or during TCB2 additions. Ruminal and mesenteric blood vessel segments were collected from Holstein steers (n=8; 659 ± 21 kg). Isolated vessel segments were incubated in Krebs-Henseleit buffer containing 0, 0.01 or 1 mM ERV for 2 h prior to TCB2 dose response or exposed to ERV concentrations simultaneously during TCB2 dose response. Vessels were suspended in a multi-myograph containing 5 mL of continuously oxygenated Krebs-Henseleit buffer and equilibrated to 1g tension for 90 min. Vessels were exposed to increasing concentrations of TCB2 every 15 min and contractile response data were normalized as a percentage of the maximum contractile response induced by 120 mM KCl reference. Analysis of variance was evaluated separately for each vessel and ERV experiment using mixed models procedure of SAS for effects of TCB2 and ERV concentrations. All blood vessels with previous ERV exposure had significantly lower contractile responses to TCB2 (P<0.01). All blood vessels with simultaneous exposure to 1 mM ERV had higher (P<0.01) contractile responses at lower concentrations of TCB2. Simultaneous ERV addition at 1x10-4 M TCB2 did not affect contractility of RV, MA, MV (P>0.05), but decreased contractility of RA (P<0.01). These results suggest ergot alkaloid exposure influences contractility of bovine ruminal and mesenteric blood vessels through serotonin receptor subtype 5HT2A by acting as both an agonist and antagonist.