During the Middle Ages, there were numerous incidences of human toxicosis involving hallucinations, convulsions, delusions, and gangrene. The syndrome became known as St. Anthony's fire. In some instances, people actually jumped from buildings during hallucinogenic states. Barger (1931) determined that ergot alkaloids from the Claviceps purpurea (Fr.) Tul. fungus were the causative agent. Ergot alkaloids (see Chapter 13) are characterized by an indole group, which is a component of a tricyclic ring known as an ergoline ring (Lorenz, 1979). Most of the sclerotia, containing the ergot bodies, can be removed during the grain cleaning process. However, small amounts have been detected in a variety of grains destined for human consumption (Scott et al., 1992). Therefore, even with modern grain processing methods, ergot alkaloids pose some threat to the human population.

Interaction of Ergot Alkaloids with Receptors

Ergot alkaloids exhibit a high affinity for a-adrenoreceptors, D2 dopamine receptors, and several subtypes of 5-HT receptors (Pertz and Eich, 1999). The various alkaloids may act as receptor agonists or antagonists, depending on the receptor and the particular alkaloid. Ergovaline was shown to activate 5-HT2A receptors and thus induce contractions of blood vessels (Dyer, 1993). As a result, blood flow to the vascular beds was reduced. Further research by Schoning et al. (2001) confirmed the interaction of ergovaline with 5-HTIB/ID and a-adrenoreceptors. Many of the toxic effects of ergot alkaloids can be explained by changes in vascular blood flow (see Chapter 12), as proposed by Cross (1997). Strickland et al. (1994) reported that ergovaline was a D2 dopamine receptor agonist in rat pituitary cells. In that study, ergovaline blocked the release of prolactin (PRL) by cultured pituitary cells. The D2 dopamine receptor antagonist, domperidone, prevented the PRL-lowering effect of ergovaline. Therefore, the effects of ergot alkaloids in milk production and agalactia probably can be explained by their effect on D2 dopamine receptors.

Effect of Ergot Alkaloids on the Immune System

Immunologists generally agree that recent evidence suggests a balance between PRL and glucocorticoids is important in regulating the immune response. Numerous studies have reported a reduction in PRL levels when ergot alkaloids are consumed (reviewed by Cross et al., 1995). Natural killer cell activity is suppressed by several dopamine receptor antagonists (huxthine, fluphenazine, pimoicide, and aalopeudal), in a PRL-dependent manner (Fiserova and Pospisil, 1999). They theorized an interaction among ergot alkaloids, lymphoid cells, and tumor cells based on indirect findings: (i) expression of dopamine, serotonin, a-adrenoreceptors, or lymphocytes that can be involved in the action of ergopeptines; (ii) inhibition of signaling pathways through intracellular enzymes (serin/heronin kinases, Ras-MAPK), leading to mitogenesis by activation of the adenylate cyclase system (D2 agonistic, PRL inhibitory eeroglines); (iii) interaction with the nuclear structures or direct binding with DNA, including derivatives of agroclavine, festuclavine, and several ergopeptines (LSD, ergosine, ergosinine, and dihydroergosine).

Toxicity of the Ergot Alkaloids of Neotyphodium coenophialum

Since its release in 1942 (see Chapter 1) ‘Kentucky 31' tall fescue seed has been used widely by livestock producers and the turfgrass industry. It is tolerant of a wide range of soil types (see Chapter 3), persistent under heavy traffic and overgrazing, and relatively drought and pest resistant (see Chapter 4, Chapter 8, Chapter 9, and Chapter 10) when compared with other pasture grasses (Siegel et al., 1984). After its release, it was observed that cattle consuming the grass did not perform as well as predicted (see Chapter 16) by the nutritional analysis of the forage (see Chapter 11). Instead, tall fescue began to gain a reputation for causing reproductive problems and poor pre- and post-weaning calf performance. Cattle consuming tall fescue during hot summer months appeared to be more stressed than normal and frequently stood in water or created mud wallows. Occasionally, lameness was detected, and, in extreme cases, a foot would become detached, especially after cold winter weather. Horse owners also began to notice agalactia, prolonged gestations, foaling difficulties, and sometimes mare and foal deaths due to dystocia in pregnant mares grazing tall fescue pastures (Garrett et al., 1980). Bacon et al. (1977) reported the first direct association between the presence of the endophyte first observed by Neil in New Zealand (Neil, 1941) and eventually identified as N. coenophialum (Glenn et al., 1996).


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