Interaction of ergovaline with serotonin receptor 5-HT 2A in bovine ruminal and mesenteric vasculature

Ronald J. Trotta, David L. Harmon, James L. Klotz

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Ergot alkaloids from endophyte- infected (Epichloë coenophiala) tall fescue (Lolium arundinaceum) induce vasoconstriction. Previous work has shown that serotonin receptor subtype, 5HT 2A , 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 5HT 2A , the vasoactivity of an agonist selective for 5HT 2A , (4-bromo-3,6-dimethoxybenzocyclobuten- 1-yl) methylamine HCl (TCB-2), was evaluated using bovine ruminal and mesenteric arteries and veins (RA, RV, MA, MV) that were exposed to ergovaline (ERV) prior to or during the TCB-2 additions. Ruminal and mesenteric blood vessel segments were collected, cleaned, and cut into 2- to 3-mm cross-sections. Vessel segments were incubated in Krebs-Henseleit buffer containing 0, 0.01 or 1 μM ERV for 2 h prior to TCB-2 dose response or exposed to ERV concentrations simultaneously during TCB-2 dose response. For the dose response portion of the study, vessels were suspended in a multimyograph containing 5 mL of continuously oxygenated Krebs-Henseleit buffer and equilibrated to 1 g tension for 90 min. Vessels were exposed to increasing concentrations of TCB-2 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 each ERV exposure experiment using the mixed models procedure of SAS for effects of TCB-2 and ERV concentrations. All blood vessels with previous ERV exposure had significantly lower contractile responses to TCB-2 (P < 0.01). All blood vessels with simultaneous exposure to 1 μM ERV had higher (P < 0.01) contractile responses at lower concentrations of TCB-2. Simultaneous ERV addition at 1 × 10 -4 M TCB-2 did not affect contractility of RV, MA, MV (P > 0.05), but decreased contractility of RA (P < 0.01). These results indicate that ergopeptine alkaloid exposure influences contractility of bovine ruminal and mesenteric blood vessels through serotonin receptor subtype 5HT 2A by acting as both an agonist and antagonist. Additional work is needed to determine if ergot alkaloids like ERV simply occupy receptor binding sites competitively, or influence receptor internalization to cause the observed divergent responses.

Original languageEnglish
Pages (from-to)4912-4922
Number of pages11
JournalJournal of Animal Science
Volume96
Issue number11
DOIs
StatePublished - Nov 21 2018

Bibliographical note

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved.

Keywords

  • Bovine
  • Mesenteric artery and vein
  • Ruminal artery and vein
  • Serotonin
  • Vasoconstriction

ASJC Scopus subject areas

  • Food Science
  • Animal Science and Zoology
  • Genetics

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