title: Antagonism of lateral saphenous vein serotonin receptors from steers grazing endophyte-free, wild-type, or novel endophyte-infected tall fescue.
abstract: Pharmacologic profiling of serotonin (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, 5HT, 5HT2A, and 5HT7 agonists. To determine if 5HT receptor activity of tall fescue alkaloids is affected by grazing endophyte-free (EF), wild-type [Kentucky-31 (KY31)], novel endophyte AR542-infected (MAXQ), or novel endophyte AR584-infected (AR584) 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) or 5HT7 (SB-269970) receptors. Biopsies were conducted over 2 yr on 35 mixed-breed steers (361.5 ± 6.3 kg) grazing EF (n = 12), KY31 (n = 12), MAXQ (n = 6), or AR584 (n = 5) pasture treatments (3 ha) between 84 and 98 d (Yr 1) or 108 to 124 d (Yr 2). Segments (2 to 3 cm) of vein were surgically biopsied, sliced into 2- to 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, ergovaline, and ergovaline + 1 × 10(-5) M ketanserin or + 1 × 10(-6) M SB-269970 in Yr 1. In Yr 2, ergotamine and ergocornine were evaluated in presence or absence of 1 × 10(-5) M ketanserin. Contractile response data were normalized to a reference addition of 1 × 10(-4) M norepinephrine. In Yr 1, contractile response to 5HT and ergovaline were least (P < 0.05) in KY31 pastures and the presence of ketanserin greatly reduced (P < 0.05) the response to ergovaline in all pastures. However, presence of SB-269970 did not (P = 0.91) alter contractile response to ergovaline. In Yr 2, there was no difference in contractile response to ergotamine (P = 0.13) or ergocornine (P = 0.99) across pasture treatments, but ketanserin reduced (P < 0.05) the contractile response to both alkaloids. The 5HT2A receptor is involved in alkaloid-induced vascular contraction and alkaloid binding may be affected by exposure to different endophyte-fescue combinations.
authors.affiliation: USDA-ARS, Forage-Animal Production Research Unit, Lexington, KY 40506, USA. james.klotz@ars.usda.gov
authors.forename: J L
authors.initials: JL
authors.lastname: Klotz
authors.forename: G E
authors.initials: GE
authors.lastname: Aiken
authors.forename: J M
authors.initials: JM
authors.lastname: Johnson
authors.forename: K R
authors.initials: KR
authors.lastname: Brown
authors.forename: L P
authors.initials: LP
authors.lastname: Bush
authors.forename: J R
authors.initials: JR
authors.lastname: Strickland
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000818:Animals; D002417:Cattle / Q000378:metabolism*; D004032:Diet / Q000662:veterinary; D060026:Endophytes / Q000737:chemistry / Q000502:physiology*; D004873:Ergolines / Q000633:toxicity; D004876:Ergot Alkaloids / Q000633:toxicity*; D004878:Ergotamine / Q000633:toxicity; D004879:Ergotamines / Q000633:toxicity; D031751:Festuca / Q000382:microbiology*; D008129:Lolium / Q000382:microbiology*; D008297:Male; D055328:Neotyphodium / Q000737:chemistry / Q000502:physiology*; D011897:Random Allocation; D012501:Saphenous Vein / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
chemical_list: D004873:Ergolines; D004876:Ergot Alkaloids; D004879:Ergotamines; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; C076760:ergovaline; C100271:ergocornine; D004878:Ergotamine