BILL E. KUNKLE INTERDISCIPLINARY BEEF SYMPOSIUM: Physiologic effects of ergot alkaloids: What happens when excretion does not equal consumption?

Increased persistence of tall fescue (Lolium arundinaceum) infested with an endophytic fungus, Epichloe coenophiala (formerly Neotyphodium coenophialum), in forage-based agriculture has led to increased effort in understanding the negative effects caused by consumption of ergot alkaloids by animals consuming this forage. Ergot alkaloids have been shown to have an extremely short plasma half-life, but this does not necessarily equate to total clearance. Studies that measured consumption and excretion of alkaloids have demonstrated that in the case of ergovaline, less is excreted than is consumed. The fate of ergot alkaloids that leave circulation but are not excreted is not well understood. Consequently, these alkaloid balance studies have led to speculation that ergovaline might bioaccumulate in the animal. Unfortunately, few data indisputably support this outcome. Progress has been slowed by the fact that the fungus produces a multitude of different ergot alkaloids that can bind to a variety of different receptors. Binding studies have shown that ergot alkaloids have unusually slow receptor dissociation rates that have been described as irreversible and contribute to a persistent signaling effect. In vitro analyses have revealed a potential for accumulation of ergot alkaloids through repetitive exposures to low concentrations creating a depot of alkaloids available to interact with receptors. The specific high binding affinity of ergot alkaloids combined with the potential turnover of alkaloids bound nonspecifically could extend residual effects of these compounds. Interestingly, cattle exposed to ergot alkaloids in vivo have a consistently lower vascular response to agonists that target receptors known to bind ergot alkaloids. If these same receptors are blocked with an antagonist, contractile response to ergopeptine alkaloids is also reduced significantly (>60% reduction). This observation that alkaloid exposure interrupts normal function of a receptor can persist 5 to 6 wk after animals have been removed from an ergot alkaloid source (and prolactin levels have long since returned to normal). Thus, clearance of ergot alkaloids from cattle grazing pasture with ergot alkaloid-producing endophytes may occur in a similar gradual manner. Studies that improve the understanding of how cattle process ergot alkaloids will help answer the question of whether ergot alkaloids bioaccumulate.