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A Review Of Research Articles Dealing With The Potential Effects Of Er

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ÐŽ§A review of research articles dealing with the potential effects of ergot alkaloids on the growth and reproductive performance of beef cattle grazing endophytic fescue.ЎЁ


Pia A. Herring

September 20, 2001

Assignment #2

AGSC 514


Due to the enormous amounts of money that are lost yearly to tall fescue toxicosis, there have been numerous studies conducted to try and discover the specific mechanisms of action that the toxins present in the endophytic fungus Neotyphodium coenophialum follow. Researchers have looked at the effect of the alkaloids at the cellular level, as well as observing the effects of the alkaloids on physiological responses and hormonal changes. All in an effort to try and better understand the different ways that the toxins affect susceptible animals. It is believed that if the mechanisms of action are better understood, that it would be easier to determine ways to counteract the effects of the toxins, and decrease the large amounts of money lost every year to tall fescue toxicosis.


One of the studies that have been conducted to discover the mechanisms of action that the toxins follow looked at the mechanism from a cellular level. Larson et al. (1999) took commercially available ergopetides, lysergic acid amides, and pyrrolizidine alkaloids, N-acetyl and N-formylloline, and added them to cellular cultures of rat D2 Dopamine receptors to see if they would bind to the receptor sites. The D2 Dopamine receptors were chosen, because they regulate prolactin release; which if inhibited is a biological indicator of toxins present from the consumption of endophyte infected tall fescue. The D2 Dopamine receptors have also been implicated in cardiovascular, thermoregulatory, nervous, and adrenal functions, as well as H2O intake. What they found was that the ergopeptide and lysergic acid amides acted like endogenous dopamine and did bind to the receptor sites; as well as inhibiting cyclic AMP production. While at the same time the pyrrolizidine alkaloids, N-acetyl and N-formylloline, did not have an effect on the receptor sites or on cyclic AMP production. In another study, the interaction of ergovaline with 5-HT2A, 5-HT1B/1D, and alpha1 receptors in isolated arteries of the rat and guinea pig was looked at (Schoning et al., 2001). They found that the ergovaline had a powerful constrictor effect on vascular tissues, due its mediation from the activation of 5-HT2A, 5-HT1B/1D receptors. And it is this vascular constriction that affects the thermoregulatory response problems that animals having fescue toxicosis exhibit. If you take what was learned from these two studies about the interactions of the alkaloid toxins at the cellular level, you will see that the toxins are capable of binding to important receptor sites in the body. And some of these receptor sites are implicated in controlling functions that are know to be affected when fescue toxicosis is present.

Studies have also been conducted to look at the effects of the alkaloid toxins at an overall systems level. Browning and Leite-Browning (1997), looked at the effect of ergotamine tartate (ergotamine) and ergonovine maleate (ergonovine) on thermal regulation and cardiovascular function. Both of these alkaloids were separately administered intravenously (i.v.) along with saline, in a manner that would allow for each animal to be exposed to each of the treatments. What they found was that the administration of the saline produced no change in measured physiological responses. The ergotamine caused respiration rates and blood pressure to rise, and plasma prolactin concentrations to decrease by 75%. The ergonovine also caused a rise in respiration and blood pressure and a 38% decrease in plasma prolactin concentrations. In a similar study done by Osborn et al. (1992) it was found that the ergotamine added to an endophyte free diet produced similar responses to those found in cattle that consume endophyte infected fescue. The feed intake (FI), average daily gain (ADG), heart rate (HT), and peripheral temperatures (ear canal, ear tip, pastern, coronary band, & tail tip) all decreased for the endophyte infected and ergotamine/endophyte free diets for the first experiment. In the second experiment, the ergotamine/endophyte free diet FI was decreased by almost 49%, when compared to the endophyte free diet. HT was also decreased by 23 beats/min, while peripheral temperature also decreased. A rise in respiration rates and rectal temperature was also noticed for the ergotamine/endophyte free diet. But then it was thought that maybe animals that were better suited for tropical climates, or heat-tolerant breeds, would not suffer from the symptoms of tall fescue toxicosis, when feed a diet containing the alkaloids. Browning (1999) took Brahman cattle (Bos indicus) feed them a fescue free diet and gave them i.v. injections of ergotamine, placed them under a heat challenge (HC) and then compared them to Hereford cattle (Bos taurus) that were placed on the same treatments. It was discovered that the Brahman cattle responded similarly to the Hereford cattle with respect to the ergotamine injections and HC.

In other studies that have been carried out, the researchers decided to look at the effect of the alkaloids on hormone levels in treated cattle. In one such study the plasma concentrations of glucagon, insulin, cortisol, and triiodothyronine (T3) were looked at when the cattle were given injections of ergotamine. Browning et al. (2000a), found that the glucagon and insulin levels changed in response to the ergotamine. In the first experiment they found that cortisol levels after the ergotamine treatment were higher than the saline treatment and pre-treatment levels for a three-hour period following ergotamine administration. Then for the next three hours the ergotamine levels were similar to those of the saline. T3 levels were higher for two hours following the ergotamine treatment, than for the saline treatment or pre-treatment levels. When the insulin levels were examined, it was found that these levels were lower than pre-treatment levels for both treatments. For the saline, the insulin levels were gradually lowered throughout the treatment. And for the ergotamine the insulin levels were lower for all eight hour following the treatment, when compared to the pre-treatment levels. As well as being lower than the saline levels for two of



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