Effects and mechanisms of action of the ergopeptides ergotamine and ergoJaline and the effects of peramine on reticulum motility of sheeP Daniel P.Poole, PhD; Raymond A. Littler, PhD;Barry L. Smith, BVSc, PhD, Lance M' Mcleay, PhD Obiective-To investigate effects and mechanisms of ergotamine and ergovaline and ef- fecis of peramine on reticulum motility of sheep' Sample population-3 sheepwith indwelling electrodes in the reticulum and samples of reticulum collected from 126sheepat an abattoir. procedure*-ln conscioussheep, motility was recordedas integratedelectromyograms irom tf'" reticulum. Ergotamine was administered lV alone or in combination with the cho- linergic muscarinic rec6ptor antagonist atropine to sheep, and motility of the reticulum was asseised. In vitro,wholb wall stri-ps of the reticulum, cut in a direction to recordlongitudinal muiJf! ictivity via force transducers, were placed in 1O-mL organ baths and superfused wiin fyroOe Ringer's solution at 37"C and oxygenated with 95% oxygen and 5% carbon dioxid6. Testing-involved incubation of reticulum strips with ergotamine, ergovaline, and oeramine and measurement of motility of the reticulum tissues. Results-Administration of ergotamine to sheep reducedthe frequencyof reticulumcon- tractions and increased baseline electromyographic activity (tonus). Frequency was un- iffected by atropine, whereastonus was significantly reduced. In vitro, ergotamine and "rgouifine'increilsed tonic contractions and stimulated phasic contractions of reticulum tisilei and potentiatedelectrically stimulatedcontractions. Atropine and tetrodotoxinre- ducedtonic contractions, but stim|lation of large-amplitude phasic contractions remained. Peramine had no effecton motility of reticulum tissues. Conclusions and Glinical Relevance-Results of the study indicated that perip_heral excit- "tory "ttectr of the ergopeptides on motility of the reticulumappear to be mediated partly throLrgh myenteric neurons and muscarinic receptors and also through direct effects on the muscles, (Am J Vet Res2009;70:270-2761 f n New Zealand, ryegrass is the dominant pasture spe- Lcies and is usually infected with the symbiotic fungus Neotyphodiumlolii. Tlnis endophyte produces a number of chemicals of consequence to New Zealand agricul- ture. The pyrrolopl'raiine alkaloid peramine provides resistance -tb ittsect attack.l Indole-diterpenoid trem- orgens (ie, the lolitrems) are responsible for perennial ryEgruss staggers,2 and the vasoactive ergopeptides (er- gotimine arid ergovaline) are responsible for the same r:y'ndromes as those associatedwith toxicoses attribut- able to fescue and ergot.3 Received December 9, 2007. Accepted May 13, 2008. From the Dqrartment of Biological Sciences, School of Science and Engineerin! (Poole, Mcleay), and Department of Statistics, School of Lo-putittg and Mathematical Sciences (Littler), University of Waikato, erivate eag 3105, Hamilton 3216, New Zealand; and Food Science Group, AgResearch, Ruakura Research Centre' Private Bag 3123, Hamilton 3216, New Zealand (Srnith). Dr Poole's present ad- dress is Department of Surgery School of Medicine, University of Califomia, San Francisco, CA 94143-0660. Dr Smith's present ad- dress is 56 Orchard Ave, Hamilton 3214, New Zealand. The authors thank Margaret Auger for assistance with care of the animals. Address correspondence to Dr. Mcleay. 5-HT ECuo EFS EMG AeanevlanoNs 5-hydroxytryptamine Median effective concentration Electrical field stimulation Electromyography Ryegrass staggers is a recognized slmdrome of herbivoies in New Zealand. Ruminants grazing endo- phyte-infected ryegrass containing the ergopeptides also have a svndrome identical to toxicosis attribut- able to ingesiion of fescue and may have hlperther- mia, inappetance, and reduced milk production-a'5 As a consequence of the aforementioned syndromes in New Zealand, our laboratory group is investigating the pathophysiologic characteristics of these mY99 toxiioses in-cottsCious sheep. We have reported6a that the tremorgens paxilline and lolitrem B have marked excitatory effects on EMG activity of skel- etal muscle of conscious sheep and excitatory and in- hibitory effects on activity of gastrointestinal smooth muscle of sheep. We have also found that the ergo- peptides ergotamine and ergovaline increase blood pr"sn.", reipiration rate, and body temperature of 274 AJVR,VoI 70, No.2, FebruarY 2009