scholarly journals PSVII-33 Determination of serotonergic receptor profiles in equine palmar artery and vein and uterine artery

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 312-313
Author(s):  
James Klotz ◽  
Karen McDowell
Keyword(s):  
Blood Vessels ◽  
Cross Sections ◽  
Uterine Artery ◽  
Serotonin Receptor ◽  
Contractile Response ◽  
Ergot Alkaloids ◽  
Fungal Endophyte ◽  
Fescue Toxicosis ◽  
Receptor Subtypes ◽  
Randomized Design

Abstract Ergot alkaloids are secondary metabolites produced by the fungal endophyte (Epichloë coenophiala) found in tall fescue (Lolium arundinaceum). Previous research has demonstrated that ergot alkaloids are vasoactive in equine palmar artery and vein but less in uterine artery. Work in cattle has shown that ergot alkaloids interact with serotonin receptors causing prolonged vasoconstriction associated with fescue toxicosis. The objective of this study was to pharmacologically assess vasoactivity of equine palmar artery and vein and uterine artery using selective agonists for serotonin receptor subtypes 5HT1B, 1D, 2A, 2B, and 7. Following euthanasia, palmar arteries, veins and uterine arteries were collected from 6 mixed breed mares. Blood vessels were separated, cleaned of external connective and adipose tissue, divided into 2–3 mm cross-sections and suspended in multi-myograph chambers containing continuously oxygenated Krebs-Henseleit buffer (95%O2/5%CO2; pH=7.4; 37°C). Following a 90-min equilibration of vascular tension and recovery from a reference addition of 1x10-4 M norepinephrine, increasing concentrations of agonists CP 93129 dihydrochloride (5HT1B), PNU 142633 (5HT1D), and TCB-2 (5HT2A) were added in 15-min intervals to assess to role of these receptors in vasoconstriction. Agonists BW 723C86 (5HT2B) and LP 44 (5HT7) were added to blood vessels precontracted with 1x10-4 M ergonovine to assess these receptors and vasorelaxation. Data were normalized as percent contractile response induced by the reference additions and analyzed as a completely randomized design using SAS. The agonists for 5HT1B and 1D did not induce a contractile response in any blood vessels tested (P > 0.05). The agonist for 5HT2A induced contractile response in all vessels tested (P < 0.05). The agonists for 5HT2B and 7 did not induce vasorelaxation different from ergonovine control (only vehicle additions) (P > 0.05). These results indicate that future work with ergot alkaloid induced vasoconstriction in equine vasculature should target the 5HT2A receptor.

scholarly journals PSII-24 Assessment of the contractility of bovine lateral saphenous and digital veins in response to ergot alkaloids

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 375-375
Author(s):  
James L Klotz ◽  
Hannah Stokley ◽  
Huihua Ji ◽  
Nabanita Chattopadhyay ◽  
David L Harmon
Keyword(s):  
Blood Vessels ◽  
Cross Sections ◽  
Saphenous Vein ◽  
Contractile Response ◽  
Ergot Alkaloids ◽  
Peripheral Vasculature ◽  
Response Data ◽  
Randomized Design ◽  
Representative Model ◽  
The Impact

Abstract Decreased blood flow caused by vasoconstriction is a hallmark of ergot alkaloid exposure. Previous research has utilized the cranial branch of the lateral saphenous vein as a model to characterize the impact of ergot alkaloids on bovine peripheral vasculature. The digital vein is more distal and closer to the hoof where damage caused by vasoconstriction occurs and may be more sensitive to ergot alkaloids. Thus, the objective was to compare contractility of the bovine lateral saphenous vein and the digital vein to increasing concentrations of ergot alkaloids. Blood vessels were collected from Holstein steers at slaughter (n = 12; 551 ±29 kg), cleaned, cut into 2-mm cross-sections, and mounted in a multi-myograph. In the myograph blood vessels were submersed in continuously gassed (95% O2/5% CO2) Krebs-Henseleit buffer. Following a 1.5-hr tension equilibration, blood vessels were exposed to a reference dose of 1x10-4 M norepinephrine. Digital and lateral saphenous veins from each steer were then exposed to increasing concentrations of a-ergocryptine (ERP), ergotamine (ERT), ergocristine (ERS), ergocornine (ERO), ergonovine (ERN), tall fescue seed extract (EXT; dilutions based on measured ergovaline concentration), lysergic acid (LSA), and lysergol (LYS) were diluted to final concentrations for use in the tissue bath of 5x10-10 to 1x10-4 M. All resultant contractile response data were normalized as a percentage of the 1x10-4 M norepinephrine response and analyzed as randomized design for effects of vein and alkaloid concentration. The maximal contractile response induced by EXT, ERT, ERO, ERS, and ERP did not differ by vein type and EXT was the most vasoactive alkaloid. The response to ERN was greater for the saphenous than the digital vein (P = 0.03) and LYS and LSA did not differ (P >0.05). These data confirm that the cranial branch of lateral saphenous vein is a representative model of peripheral vasculature of the bovine hindlimb.

scholarly journals Influence of Prolonged Serotonin and Ergovaline Pre-Exposure on Vasoconstriction Ex Vivo

Toxins ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 9
Author(s):  
Eriton E. L. Valente ◽  
David L. Harmon ◽  
James L. Klotz
Keyword(s):  
Blood Vessels ◽  
Ergot Alkaloid ◽  
Inhibitory Concentration ◽  
Contractile Response ◽  
Ex Vivo ◽  
Ergot Alkaloids ◽  
Exposure Period ◽  
Inhibitory Response ◽  
Previous Exposure ◽  
Ic50 Concentration

Ergot alkaloid mycotoxins interfere in many functions associated with serotonergic neurotransmitters. Therefore, the objective was to evaluate whether the association of serotonin (5-hydroxytryptamine, 5-HT) and ergot alkaloids during a 24 h pre-incubation could affect the vascular contractile response to ergot alkaloids. To evaluate the effects of 24 h exposure to 5-HT and ergot alkaloids (ergovaline, ERV), two assays were conducted. The first assay determined the half-maximal inhibitory concentration (IC50) following the 24 h pre-exposure period, while the second assay evaluated the effect of IC50 concentrations of 5-HT and ERV either individually or in combination. There was an interaction between previous exposure to 5-HT and ERV. Previous exposure to 5-HT at the IC50 concentration of 7.57 × 10−7 M reduced the contractile response by more than 50% of control, while the exposure to ERV at IC50 dose of 1.57 × 10−10 M tended to decrease (p = 0.081) vessel contractility with a response higher than 50% of control. The 24 h previous exposure to both 5-HT and ERV did not potentiate the inhibitory response of blood vessels in comparison with incubation with each compound alone. These results suggest receptor competition between 5-HT and ERV. More studies are necessary to determine the potential of 5-HT to treat toxicosis caused by ergot alkaloids.

scholarly journals Assessment of the vasoactive effects of the (S)-epimers of ergot alkaloids in vitro

2020 ◽  
Vol 98 (7) ◽  
Author(s):  
Jensen E Cherewyk ◽  
Sarah E Parker ◽  
Barry R Blakley ◽  
Ahmad N Al-Dissi
Keyword(s):  
Cross Sections ◽  
Contractile Response ◽  
Ergot Alkaloids ◽  
Biologically Active ◽  
Beef Steers ◽  
Total N ◽  
Major Mechanism ◽  
Mixed Breed ◽  
Widespread Belief

Abstract Ergot alkaloids are produced by the fungus Claviceps purpurea and their levels are carefully monitored in animal and human diets due to their harmful effects and widespread contamination of cereal crops. Ergot alkaloids exist in two forms known as the (R)- and (S)-epimers with only the former being monitored in diets in North America. The (S)-epimers of ergot alkaloids are thought to be biologically inactive and, therefore, harmless. A major mechanism by which the (R)-epimers of ergot alkaloids produce their toxic effect is through vasoconstriction. Therefore, the objective of this study was to examine the vasoactivity potential (contractile response) of four (S)-epimers, namely ergocryptinine, ergocristinine, ergocorninine, and ergotaminine utilizing an in vitro arterial tissue bath system. Bovine metatarsal arteries (n = 6, ergocryptinine and ergocorninine; n = 6, ergocristinine and ergotaminine; n = 6 arteries/(S)-epimer, total n = 12) were collected from healthy mixed-breed beef steers immediately after slaughter, cut into 3-mm arterial cross sections, and suspended in a tissue bath with continuously oxygenated Krebs–Henseleit buffer. To assess the contractile response of each (S)-epimer, a cumulative contractile dose–response curve was constructed by incubating arteries with increasing concentrations (1 × 10−11 to 1 × 10−6 M) of that (S)-epimer. Contractile responses were recorded as grams of tension and were normalized to an initial contraction of phenylephrine. Contrary to the widespread belief, all tested (S)-epimers were found vasoactive and produced a concentration-dependent arterial contractile response similar to what has been reported for the (R)-epimers. The arterial contractile response to ergotaminine was strongest and was significantly greater than that of ergocryptinine and ergocristinine at the highest concentration used (P ≤ 0.01). Our results indicate that the (S)-epimers are biologically active and are likely harmful similar to the (R)-epimers. The levels of (S)-epimers should be carefully monitored in human and animal diets worldwide.

Effects of Aminocyclopyrachlor Plus Metsulfuron on Tall Fescue Yield, Forage Quality, and Ergot Alkaloid Concentration

2016 ◽  
Vol 30 (1) ◽  
pp. 171-180 ◽  
Author(s):  
Trevor D. Israel ◽  
Gary E. Bates ◽  
Thomas C. Mueller ◽  
John C. Waller ◽  
G. Neil Rhodes
Keyword(s):  
Tall Fescue ◽  
Ergot Alkaloid ◽  
Crude Protein ◽  
Ergot Alkaloids ◽  
Forage Quality ◽  
The United States ◽  
Fungal Endophyte ◽  
Fescue Toxicosis ◽  
Protein Levels ◽  
Spring Harvest

Most tall fescue in the United States is infected with a fungal endophyte which imparts certain advantages to the plant, such as drought tolerance, insect feeding deterrence, and enhanced mineral uptake. However, the endophyte also produces ergot alkaloids that are harmful to livestock and contribute to fescue toxicosis. Because the alkaloids are concentrated in seed and stems, a potential way to reduce the likelihood of fescue toxicosis is by suppressing seedhead formation with herbicides. Research was conducted from 2012 to 2014 using metsulfuron applied alone and in combination with other herbicides in spring to determine the growth response of tall fescue, effects on forage quality, and ergot alkaloid concentration. Clipping or metsulfuron applied alone or in combination with aminocyclopyrachlor or aminopyralid reduced seedhead density by 36 to 55% compared to the nontreated control. Treatments containing metsulfuron reduced spring harvest yield 35 to 61%, but no differences were observed in the summer or year-after harvests. The same treatments increased crude protein levels by 1.03 to 2.14% and reduced acid detergent fiber levels by 1.60 to 2.76% compared to the nontreated control at spring harvest. Treatments containing metsulfuron reduced ergot alkaloid concentration 26 to 34% at the spring harvest, but no differences were observed in summer-harvested forage. Results from this study indicate metsulfuron applied alone or in combination with aminocyclopyrachlor or aminopyralid can potentially reduce the severity of fescue toxicosis and improve forage quality.

scholarly journals Effects of different vasopressors on the contraction of the superior mesenteric artery and uterine artery in rats during late pregnancy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingting Wang ◽  
Limei Liao ◽  
Xiaohui Tang ◽  
Bin Li ◽  
Shaoqiang Huang
Keyword(s):  
Caesarean Section ◽  
Blood Vessels ◽  
Mesenteric Artery ◽  
Uterine Artery ◽  
Contractile Response ◽  
Mesenteric Arteries ◽  
Response Curves ◽  
Pregnant Rats ◽  
Neuraxial Anaesthesia ◽  
Significant Difference

Abstract Background Hypotension after neuraxial anaesthesia is one of the most common complications during caesarean section. Vasopressors are the most effective method to improve hypotension, but which of these drugs is best for caesarean section is not clear. We assessed the effects of vasopressors on the contractile response of uterine arteries and superior mesenteric arteries in pregnant rats to identify a drug that increases the blood pressure of the systemic circulation while minimally affecting the uterine and placental circulation. Methods Isolated ring segments from the uterine and superior mesenteric arteries of pregnant rats were mounted in organ baths, and the contractile responses to several vasopressor agents were studied. Concentration-response curves for norepinephrine, phenylephrine, metaraminol and vasopressin were constructed. Results The contractile response of the mesenteric artery to norepinephrine, as measured by the pEC50 of the drug, was stronger than the uterine artery (5.617 ± 0.11 vs. 4.493 ± 1.35, p = 0.009), and the contractile response of the uterine artery to metaraminol was stronger than the mesenteric artery (pEC50: 5.084 ± 0.17 vs. 4.92 ± 0.10, p = 0.007). There was no statistically significant difference in the pEC50 of phenylephrine or vasopressin between the two blood vessels. Conclusions In vitro experiments showed that norepinephrine contracts peripheral blood vessels more strongly and had the least effect on uterine artery contraction. These findings support the use of norepinephrine in mothers between the time of neuraxial anaesthesia and the delivery of the foetus.

Microarray evaluation of bovine hepatic gene response to fescue toxicosis

2013 ◽  
Vol 6 (4) ◽  
pp. 419-426 ◽  
Author(s):  
D.D. Tanaree ◽  
J.M. Duringer ◽  
D.W. Bohnert ◽  
A.M. Craig
Keyword(s):  
Gene Expression ◽  
Cardiac Development ◽  
Cell Cycle Control ◽  
Average Daily Gain ◽  
Regulation Of Gene Expression ◽  
Clinical Signs ◽  
Ergot Alkaloids ◽  
Fungal Endophyte ◽  
Fescue Toxicosis ◽  
Cellular Mechanisms

‘Fescue toxicosis’ is a disease in livestock caused by ingestion of ergot alkaloids produced by the fungal endophyte Neotyphodium coenophialum in tall fescue; it is estimated to cost 1 billion USD in damages per year to the beef industry alone. Clinical signs include decreased reproductive fitness, necrosis of extremities, and reduced average daily gain and milk production. Little is known about the cellular mechanisms that mediate these toxic sequelae. We evaluated the effects of ergovaline-based fescue toxicosis on gene expression via oligonucleotide microarray. Liver biopsies were obtained from steers (n=4) pre- and post-exposure (0 and 29 days) to feed containing 579 ng/g ergovaline. Analyses were performed using both ANOVA with false discovery rate correction and Storey's optimal discovery procedure. Overall, down-regulation of gene expression was observed; heart contraction and cardiac development, apoptosis, cell cycle control, and RNA processing genes represented the bulk of differentially expressed transcripts. 2 CYPs (CYP2E1 and CYP4F6) were amongst the significantly upregulated results. Thus, exposure of cattle to toxic levels of ergovaline caused widespread changes in hepatic gene expression, which can both help explain macroscopic clinical signs observed in ruminant animals, and reinforce previous findings in monogastric models.

scholarly journals Vasoactive Effects of Acute Ergot Exposure in Sheep

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 291
Author(s):  
Rossalin Yonpiam ◽  
Jair Gobbet ◽  
Ashok Jadhav ◽  
Kaushik Desai ◽  
Barry Blakley ◽  
...  
Keyword(s):  
Single Dose ◽  
Chronic Exposure ◽  
Contractile Response ◽  
Ergot Alkaloids ◽  
Acute Exposure ◽  
Control Group ◽  
Vascular Effects ◽  
Adrenergic Antagonist ◽  
Vascular Sensitivity ◽  
Dose Dependent

Ergotism is a common and increasing problem in Saskatchewan’s livestock. Chronic exposure to low concentrations of ergot alkaloids is known to cause severe arterial vasoconstriction and gangrene through the activation of adrenergic and serotonergic receptors on vascular smooth muscles. The acute vascular effects of a single oral dose with high-level exposure to ergot alkaloids remain unknown and are examined in this study. This study had two main objectives; the first was to evaluate the role of α1-adrenergic receptors in mediating the acute vasocontractile response after single-dose exposure in sheep. The second was to examine whether terazosin (TE) could abolish the vascular contractile effects of ergot alkaloids. Twelve adult female sheep were randomly placed into control and exposure groups (n = 6/group). Ergot sclerotia were collected and finely ground. The concentrations of six ergot alkaloids (ergocornine, ergocristine, ergocryptine, ergometrine, ergosine, and ergotamine) were determined using HPLC/MS at Prairie Diagnostic Services Inc., (Saskatoon, SK, Canada). Each ewe within the treatment group received a single oral treatment of ground ergot sclerotia at a dose of 600 µg/kg BW (total ergot) while each ewe in the control group received water. Animals were euthanized 12 h after the treatment, and the pedal artery (dorsal metatarsal III artery) from the left hind limb from each animal was carefully dissected and mounted in an isolated tissue bath. The vascular contractile response to phenylephrine (PE) (α1-adrenergic agonist) was compared between the two groups before and after TE (α1-adrenergic antagonist) treatment. Acute exposure to ergot alkaloids resulted in a 38% increase in vascular sensitivity to PE compared to control (Ctl EC50 = 1.74 × 10−6 M; Exp EC50 = 1.079 × 10−6 M, p = 0.046). TE treatment resulted in a significant dose-dependent increase in EC50 in both exposure and control groups (p < 0.05 for all treatments). Surprisingly, TE effect was significantly more pronounced in the ergot exposed group compared to the control group at two of the three concentrations of TE (TE 30 nM, p = 0.36; TE 100 nM, p < 0.001; TE 300 nM, p < 0.001). Similar to chronic exposure, acute exposure to ergot alkaloids results in increased vascular sensitivity to PE. TE is a more potent dose-dependent antagonist for the PE contractile response in sheep exposed to ergot compared to the control group. This study may indicate that the dry gangrene seen in sheep, and likely other species, might be related to the activation of α1-adrenergic receptor. This effect may be reversed using TE, especially at early stages of the disease before cell death occurs. This study may also indicate that acute-single dose exposure scenario may be useful in the study of vascular effects of ergot alkaloids.

scholarly journals Effects of management system on beef heifer growth and reproductive performance

2020 ◽  
Author(s):  
Parker A Henley ◽  
Frank A Ireland ◽  
Igor F Canisso ◽  
J Lannett Edwards ◽  
Daniel W Shike
Keyword(s):  
Development Strategy ◽  
Breeding Season ◽  
Reproductive Performance ◽  
Body Condition Score ◽  
Pregnancy Rates ◽  
Fescue Toxicosis ◽  
Soybean Hulls ◽  
Randomized Design ◽  
Condition Score ◽  
Calf Performance

Abstract This study evaluated the effect of heifer development system on body weight (BW), body condition score (BCS), fescue toxicosis symptoms, reproductive performance, and subsequent calf growth of fall-calving beef heifers. Angus × Simmental heifers [n = 399; 240 ± 20.0 kg initial BW; age = 252 ± 20 d] were stratified by BW and BCS and assigned to 1 of 12 groups in each of the 2 production years. The study utilized a stratified randomized design. Pens were randomly assigned to 4 treatments: drylot (DL) development (fed ad-libitum diet consisting of 90% hay and 10% DDGS on a dry matter basis), grazing endophyte-infected fescue supplemented daily (2.3 kg as-fed/heifer/d; 50:50 mix of soybean hulls and DDGS; E+/S), grazing endophyte-infected fescue and supplemented from the midpoint of treatment period until breeding (4.5 kg as-fed/heifer/d; 50:50 mix of soybean hulls and DDGS; E+/LS), and grazing novel endophyte-infected fescue with no supplement (NE+/NS). Treatments ceased on d 168 [time of artificial insemination (AI)] and heifers were commingled and managed as a group through second breeding season. Heifers in DL had greatest (P ≤ 0.05) BW and BCS from d 28 until d 254. Furthermore, E+/S heifers had greater (P ≤ 0.05) BW and BCS than both E+/LS and NE+/NS from d 28 until d 168. On d 56 and 84, E+/LS heifers had lower (P ≤ 0.05) BW and BCS compared to NE+/NS, but on d 148 treatments reranked and E+/LS remained at a greater (P ≤ 0.05) BW and BCS compared to NE+/NS through the first breeding season. Drylot heifers had greatest (P ≤ 0.05) percentage cycling and percentage of mature BW at AI (66.6%) and had greater (P ≤ 0.05) AI and overall pregnancy rates compared to E+/LS and NE+/NS. The E+/S (55%) and E+/LS (53.7%) heifers were developed to a greater (P &lt; 0.01) percentage of mature BW than NE+/NS (49.3%). A greater (P ≤ 0.02) percentage of DL and E+/S heifers were pregnant at the end of the first breeding season (89.3 and 85.1%; respectively) compared to NE+/NS (61.5%). In summary, DL heifers had the greatest BW and BCS at AI, percentage cycling, and AI pregnancy rate. However, this strategy did not result in differing overall pregnancy rates between DL, E+/S, and E+/LS and there were no differences in milk production, rebreeding reproductive performance, and calf performance between all treatments. Finally, the poorest AI and overall pregnancy rates of the NE+/NS heifers suggests this is not a viable development strategy for fall-born heifers.

Serotonin Receptor Subtypes: Implications for Psychopharmacology

1991 ◽  
Vol 159 (S12) ◽  
pp. 7-14 ◽  
Author(s):  
P. J. Cowen
Keyword(s):  
Cognitive Processes ◽  
Serotonin Receptor ◽  
Antidepressant Treatment ◽  
Receptor Subtypes ◽  
Therapeutic Effects ◽  
Controlled Clinical Trials ◽  
Wide Range ◽  
Selective Ligands ◽  
Coupling Mechanisms ◽  
Therapeutic Possibilities

Serotonin (5-HT) interacts with multiple brain 5-HT receptor subtypes to influence a wide range of behaviours. Three main families of 5-HT receptors (5-HT1, 5-HT2 and 5-HT3) have been described which differ in their binding affinity for selective ligands, their receptor-effector coupling mechanisms, and the behavioural processes they regulate. Nevertheless, manipulation of several different 5-HT receptor subtypes (5-HT1A, 5-HT1c, 5-HT2 and 5-HT3) may produce anxiolytic effects; 5-HT1A and 5-HT2 receptors may be involved in the aetiology of major depression and the therapeutic effects of antidepressant treatment; and 5-HT3 receptors have been linked to reward mechanisms and cognitive processes. These advances offer therapeutic possibilities, the value of which can only be satisfactorily assessed by controlled clinical trials.

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