Author
|
Submitted to: American Society of Animal Science Southern Section Meeting
Publication Type: Abstract Only Publication Acceptance Date: 10/31/2014 Publication Date: 2/2/2015 Citation: Klotz, J.L. 2015. Physiologic effects of ergot alkaloids: What happens when excretion does not equal absorption?. American Society of Animal Science Southern Section Meeting. Pg. 92. Interpretive Summary: Technical Abstract: Increased persistence of tall fescue (Lolium arundinaceum) infested with an endophytic fungus Epichloë 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 excretion. Studies that measured alkaloids consumed and excreted 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 can bioaccumulate in the animal. Unfortunately, there are no in vivo data that 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. Multiple in vitro studies have shown that ergopeptine alkaloids (like ergovaline) have a persistent receptor-binding effect that results in a sustained contractile response and the consequence is the vasoconstriction associated with fescue toxicosis. If binding affinities of ergot alkaloids like ergovaline are sufficient to permit a post-absorptive accumulation, then a gradual build up may occur through chronic exposure to ergot alkaloids achieved by grazing. Myographic and mass spectrometric analyses have revealed a potential for vascular accumulation of ergot alkaloids through repetitive exposures to low concentrations. 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). Recent experiments have demonstrated that prior exposure of blood vessels to ergovaline completely abolishes the ability of the blood vessel to respond to similar alkaloids like ergotamine. This observation that alkaloid exposure interrupts the normal function of a receptor can persist 5 to 6 weeks 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 that were grazing pasture with ergot alkaloid-producing endophytes may occur in a similar gradual manner. This may or may not be detectable if only prolactin were measured. Studies that improve the understanding of how cattle process ergot alkaloids will help answer the question of whether ergot alkaloids bioaccumulate. |
