Ergot alkaloids (EAs) are toxic substances naturally produced by Claviceps fungi. These fungi infest a wide range of cereals and grasses. When domestic animals are exposed to EAs through contaminated feeds, it is detrimental to them and leads to significant economic losses. For that reason, it is important to monitor feed for the presence of EAs, especially with methods enabling their determination in processed materials.

Direct evidence linking alkaloids found in endophyte-infected tall fescue forage with the livestock disorder known as fescue toxicosis is lacking. Physiologic effects of fescue toxicosis include reduced serum prolactin concentration in cattle. A monoclonal antibody specific to the lysergic moiety of ergot alkaloids was developed in mice after creating an immunogen by linking lysergol to human serum albumin. The antibody was specific to the lysergic moiety and, therefore, it cross-reacted with ergot alkaloids, lysergic acid, and lysergol. The antibody did not cross-react with alkaloid derivatives that had bromated or hydrogenated lysergic ring moieties. Fescue toxicosis conditions were elicited in yearling Angus steers by permitting them to graze endophyte-infected tall fescue containing > 650 Kg/kg of ergovaline for 60 days. Passive immunization of steers by infusion of the monoclonal antibody increased serum prolactin concentration by 7 ng/ml, beginning immediately after infusion. Control steers did not respond to treatment with bovine serum albumin. Active immunization of yearling Angus heifers with immunogens containing lysergol or ergonovine linked to human serum albumin resulted in an antibody response.

Cultured rat pituitary cells were studied to: determine the effects of ergovaline and loline on in vitro prolactin release; delineate the agonistic activity of these alkaloids at the D2 dopamine receptor, using 2 selective D2 dopamine receptor antagonists; and compare the efficacy of 2 dopamine receptor antagonists in reversing effects of the treatments on in vitro prolactin secretion. Ergovaline reduced in vitro prolactin release by at least 40% (P < 0.05) at concentrations of 10(-4),10(-6), and 10(-8) M. However, loline reduced (P < 0.05) prolactin release only at the highest concentration, 10(-4) M. Two standard dopamine agonists, dopamine and alpha-ergocryptine, were used to verify that the inhibitory control mechanisms of in vitro prolactin release were intact. Both compounds reduced prolactin release by at least 40% for concentrations of 10(-4), 10(-6), or 10(-8) M. Selective D2 dopamine receptor antagonists 10(-6) M, domperidone and sulpiride, reversed (P < 0.05) the effect of loline on in vitro prolactin release. However, only domperidone (10(-6) M) was able to reverse (P < 0.05) the effect of ergovaline and only at the lowest ergovaline concentration (10(-8) M). Domperidone was more effective (P < 0.05) in reversing the prolactin-suppressing effect of alpha-ergocryptine than was sulpiride. The dose-response curve for domperidone (cubic fit, P < 0.0001) indicated a threshold concentration (10(-7)M) for reversal of alpha-ergocryptine's (10(-8)M) effect on prolactin release. However, at similar concentration of sulpiride (quadratic fit, P < 0.007), a threshold level was not obtained. These data indicate that ergovaline and loline mayact as D2 dopamine receptor agonists. Additionally, domperidone seems to be a more potent drug for reversal of the alkaloids hypoprolactinenic effect in vitro than does sulpiride.

We determined the vasoconstrictive effects of selected ergot alkaloids, and a sample containing loline and its derivative alkaloids, on the isolated dorsal pedal vein of cattle, as a model system to study one of the toxic effects that result from cattle ingesting fescue forage infected with the endophytic fungus Acremonium coenophialum. The ergot compounds ergotamine, ergosine, and agroclavine constricted this peripheral vein of cattle, but much less so than did the alpha-adrenergic agonist norepinephrine, which supports the ergots acting as partial agonists for these receptors. However, the sample of loline and loline-derivative alkaloids did not affect the dorsal pedal vein when given at concentrations similar to those of the ergot compounds. Loline and loline-derivative alkaloid sample at high concentrations partially inhibited norepinephrine-elicited vascular contraction, an effect that appeared to be unrelated to alpha-adrenoceptor activity. Thus, in the dorsal pedal vein model in cattle, the ergopeptide alkaloids were more venoconstrictive than were loline and its derivative alkaloids.