Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/29/2013
Publication Date: 7/3/2013
Citation: Klotz, J.L., Aiken, G.E., Johnson, J.M., Brown, K.R., Bush, L.P., Strickland, J.R. 2013. Antagonism of lateral saphenous vein serotonin receptors from steers grazing endophyte-free, wild-type, or novel endophyte-infected tall fescue. Journal of Animal Science. 91:4492-4500. Interpretive Summary: The serotonin (5HT) receptor 5HT2A is involved in the tall fescue alkaloid-induced vascular contraction in the bovine periphery. This was determined by evaluating the contractile responses of lateral saphenous veins biopsied from cattle grazing different tall fescue/endophyte combinations. The contractile responses of the biopsied blood vessel segments to different alkaloids (ergovaline, ergotamine, and ergocornine) were evaluated in the presence or absence of an antagonist or blocker of the 5HT2A receptor. The presence of the antagonist significantly reduced the contractile response to all three alkaloids in all three pasture types. A better understanding of how tall fescue alkaloids cause peripheral vasoconstriction will lead to better solutions for summer slump and fescue foot manifestations of the fescue toxicosis syndrome.
Technical Abstract: Pharmacologic profiling of 5-hydroxytryptamine (5HT) receptors of bovine lateral saphenous vein has shown that cattle grazing endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have altered responses to ergovaline (ERV), 5HT, 5HT2A and 5HT7 agonists. To determine if 5HT receptor activity of tall fescue alkaloids is affected by grazing endophyte-free (EF), wild type (WT), or novel endophyte-infected (NE) tall fescue, contractile responses of lateral saphenous veins biopsied from cattle grazing these different fescue-endophyte combinations were evaluated in presence or absence of antagonists for 5HT2A (ketanserin; KET) or 5HT7 (SB-269970; SB) receptors. Biopsies were conducted over 2 years on 35 mixed breed steers (361.5 ' 6.3 kg) grazing KY31 (WT; n=12), EF (n=12), MAXQ (NE AR542; n=6) or KYFA9301 (NE AR584; n=5) pasture treatments (3 ha) between 84-98 d (Yr 1) or 108-124 d (Yr 2). Segments (2-3 cm) of vein were surgically biopsied, sliced into 2-3 mm cross-sections, and suspended in a myograph chamber containing 5 mL of oxygenated Krebs-Henseleit buffer (95% O2/5% CO2; pH = 7.4; 37'C). Veins were exposed to increasing concentrations of 5HT, ERV, and ERV+1x10-5 M KET, or +1x10-6 M SB in Yr 1. In Yr 2, ergotamine (ERT) and ergocornine (ERO) were evaluated in presence or absence of 10-5 M KET. Data were normalized to a reference addition of 1x10-4 M norepinephrine and analyzed as a CRD factorial with steer as experimental unit. In Yr 1, contractile response to 5HT and ERV were lowest in WT KY31 pastures (P < 0.05) and the presence of KET greatly reduced the response to ERV in all pastures (P < 0.05). The presence of SB did not alter contractile response to ERV. In Yr 2, there was no difference in response to ERO or ERT across pasture treatments, but KET again reduced the contractile response both alkaloids (P < 0.05). The 5HT2A receptor is involved in alkaloid-induced vascular contraction and alkaloid binding may be affected by exposure to different endophyte-fescue combinations.