Pharmacologic assessment of bovine ruminal and mesenteric vascular serotonin receptor populations

Authors: SNIDER, MIRIAM - UNIVERSITY OF KENTUCKY; HARMON, DAVID - UNIVERSITY OF KENTUCKY; MATTHEWS, JAMES - UNIVERSITY OF KENTUCKY; Klotz, James

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/29/2018
Publication Date: 2/7/2018
Citation: Snider, M.A., Harmon, D.L., Matthews, J.C., Klotz, J.L. 2018. Pharmacologic assessment of bovine ruminal and mesenteric vascular serotonin receptor populations. Journal of Animal Science. 96(4):1570-1578.

Interpretive Summary: Fescue toxicosis negatively affects cattle productivity in the form of decreased intake and weight gains. The compounds that responsible for causing fescue toxicosis are ergot alkaloids. Ergot alkaloids have been shown to cause vasoconstriction in the blood vessels supporting the gastrointestinal tract. This has been theorized to cause a reduction in nutrient uptake from the gut and contribute to the decreased productivity of growing cattle. The current study sought to identify what serotonin receptors are involved in ergot alkaloid-induced vasoconstriction in the rumen and small intestinal mesentery of cattle. Six different serotonin receptors were assessed for vasoactivity using selective agonists in a myograph system that measures vascular tension. It was found that serotonin receptor 2A was predominantly active across mesenteric and ruminal arteries and veins. None of the other receptors evaluated demonstrated contractile vasoactivity, however, serotonin 1D and 2B contributed to vasorelaxation in the mesenteric vein. These findings will benefit researchers as future studies are designed and conducted to further characterize the relationship between ergot alkaloids and serotonin receptors and how this contributes to fescue toxicosis.

Technical Abstract: Prior work using a contractility bioassay determined that the serotonin (5-HT) receptor subtype 5-HT2A is present in bovine lateral saphenous veins and plays a role in ergot alkaloid-induced vascular contraction in steers grazing endophyte-infected (Epichloë coenophiala) tall fescue (Lolium arundinaceum). Ergot alkaloids have also been shown to be vasoactive in bovine gut vasculature. To determine what 5-HT receptors are involved in vasoconstriction of gut vasculature, contractility of ruminal and mesenteric arteries and veins collected from cattle were evaluated in the presence of agonists selective for 5-HT1B (CP 93129) 5-HT1D (L-694, 247), 5-HT2A (TCB-2), 5-HT2B (BW 723C86), 5-HT4 (BIMU-8) and 5-HT7 (LP 44) receptors. Segments of ruminal and mesenteric veins and arteries were collected and suspended in a multi-myograph containing continuously oxygenated Krebs-Henseleit buffer. Blood vessels were exposed to increasing concentrations of 5-HT agonists every 15 min and contractile response data were normalized as a percentage of the maximum contractile response induced by 120 mM KCl. Analysis of variance was evaluated using mixed models procedure of SAS for effects of agonist concentration for each vessel type. Receptor agonists BW 723C86, L-694, 247, and LP 44 did not induce a contractile response for ruminal or mesenteric vasculature (P > 0.05). However, when exposed to BW 723C86 or L-694, 247, mesenteric veins relaxed below zero (P < 0.05). Exposure of all four vessel types to TCB-2 induced contractile responses (P < 0.05). The findings of this study indicate that 5-HT1D and 5-HT2B are present in mesenteric veins and may play a role in vasorelaxation. Further, 5-HT2A is present in ruminal and mesenteric vasculature, plays a role in vasoconstriction of these vessels, and could be influenced by ergot alkaloid exposure as has been demonstrated in peripheral blood vessels.