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Ergot Alkaloid Transport Across Ruminant Gastric Tissues N Ergot alkaloid transport across ruminant gastric tissues N. S. Hill, F. N. Thompson, J. A. Stuedemann, G. W. Rottinghaus, H. J. Ju, D. L. Dawe and E. E. Hiatt, 3rd J Anim Sci 2001. 79:542-549. The online version of this article, along with updated information and services, is located on the World Wide Web at: http://jas.fass.org www.asas.org Downloaded from jas.fass.org at USDA Natl Agricultural Library on December 17, 2008. Ergot alkaloid transport across ruminant gastric tissues N. S. Hill*,1, F. N. Thompson†, J. A. Stuedemann‡, G. W. Rottinghaus§, H. J. Ju*, D. L. Dawe†, and E. E. Hiatt, III* *Department of Crop and Soil Sciences, †College of Veterinary Medicine, University of Georgia, Athens 30602; ‡USDA-ARS J. Phil Campbell Sr. Natural Resource Center, Watkinsville, GA 30677; and §College of Veterinary Medicine, University of Missouri, Columbia 65211 ABSTRACT: Ergot alkaloids cause fescue toxicosis measured and the potential transportable alkaloids cal- when livestock graze endophyte-infected tall fescue. It culated by multiplying the moles of transported alka- is generally accepted that ergovaline is the toxic compo- loids per square centimeter of each tissue type by the nent of endophyte-infected tall fescue, but there is no surface area of the tissue. Studies were conducted to direct evidence to support this hypothesis. The objective compare alkaloid transport in reticular, ruminal, and of this study was to examine relative and potential omasal tissues and to determine whether transport was transport of ergoline and ergopeptine alkaloids across active or passive. Ruminal tissue had greater ergot al- isolated gastric tissues in vitro. Sheep ruminal and kaloid transport potential than omasal tissue (85 vs 60 omasal tissues were surgically removed and placed in mmol) because of a larger surface area. The ruminal parabiotic chambers. Equimolar concentrations of ly- posterior dorsal sac had the greatest potential for alka- sergic acid, lysergol, ergonovine, ergotamine, and ergo- loid transport, but the other ruminal tissues were not cryptine were added to a Kreb’s Ringer phosphate (KRP) solution on the mucosal side of the tissue. Tissue different from one another. Alkaloid transport was less was incubated in near-physiological conditions for 240 among reticular tissues than among ruminal tissues. min. Samples were taken from KRP on the serosal side Transport of alkaloids seemed to be an active process. of the chambers at times 0, 30, 60, 120, 180, and 240 The alkaloids with greatest transport potential were min and analyzed for ergot alkaloids by competitive lysergic acid and lysergol. Ergopeptine alkaloids tended ELISA. The serosal KRP remaining after incubation to pass across omasal tissues in greater quantities than was freeze-dried and the alkaloid species quantified by across ruminal tissues, but their transport was minimal HPLC. The area of ruminal and omasal tissues was compared to lysergic acid and lysergol. Key Words: Ergot Alkaloids, Festuca, Rumen Mucosa, Toxicity 2001 American Society of Animal Science. All rights reserved. J. Anim. Sci. 2001. 79:542–549 Introduction (1998) found that approximately 94% of the alkaloids from cattle grazing endophyte-infected tall fescue al- Livestock grazing endophyte-infected tall fescue in- kaloids were found in the urine and 6% in the bile. gest ergot alkaloids that cause the condition known Extensive research using nonruminants suggests that as fescue toxicosis (Hill et al., 1994; Bouton et al., ergopeptine alkaloids are excreted via the bile and 1998). Ergot alkaloids are grouped into two broad ergoline alkaloids are excreted through the urine (see classes: the ergoline alkaloids that contain the lysergic reviews by Nimmerfall and Rosenthaler, 1976; Eckert ring structure with hydroxyl, carboxyl, or carboxamide et al., 1978; Griffith et al., 1978). Assuming that the functional groups and the ergopeptine alkaloids that metabolic functions of the excretory organs are highly have a tripeptide cyclol moiety attached at the carbox- conserved among ruminants and nonruminants, these amide site (Rutschmann and Stadler, 1978). studies suggest that the circulating alkaloids in rumi- Little is known about bioavailability or metabolism nants grazing tall fescue are either 1) converted from of the ergot alkaloids in ruminants. Stuedemann et al. the ergopeptine form before excretion, 2) absorbed as the ergoline alkaloids, or 3) absorbed as both and me- tabolized to the ergoline prior to excretion. Urinary appearance and disappearance of ergot al- 1 Correspondence: 3111 Miller Plant Sciences Bldg. (phone: 706- kaloids occurs within 12 h following switching animals 542-0923; fax: 706-542-0914; E-mail: [email protected]). Received March 24, 2000. among endophyte-infected and endophyte-free pas- Accepted October 27, 2000. tures (Stuedemann et al., 1998). Expeditious appear- 542 Downloaded from jas.fass.org at USDA Natl Agricultural Library on December 17, 2008. Ergot alkaloid transport across tissues 543 ance and disappearance of urinary alkaloids is most Ergot alkaloids used in the experiments were a mix- likely to occur if the alkaloids are soluble in ruminal ture of lysergol, lysergic acid, ergonovine, ergocryp- fluids. Because the liquid fraction of the digesta is tine, and ergotamine tartrate. Lysergol, lysergic acid, associated with the ruminal microbial ecosystem or is and ergonovine were selected because they represent recycled in the omasum (Church, 1979; Ruckebusche the alcohol, acid, and amide forms of the ergoline alka- and Thivend, 1980), these tissues may serve as an loids, respectively. Ergocryptine and ergotamine tar- important absorptive site for the alkaloids. The objec- trate were used as the ergopeptine alkaloids. Each tive of this study was to ascertain which forms of ergot alkaloid had a final concentration of 30.5 mM in etha- alkaloids are absorbed from the digestive system by nol. Equimolar concentrations of each alkaloid were ruminal and omasal tissues. used so that transport affinities of each could be as- sessed. One-tenth milliliter of alkaloid solution was Materials and Methods administered to the mucosal chamber. Thus, the final concentration of each alkaloid in the mucosal cham- All experiments were conducted using tissues from bers was 30.5 ␮M in 10 mL of solution of the mucosal digestive tracts of Rambouillet ewe lambs (Ovis aries). side of the chamber. The serosal chamber also received The ewes were approximately 8 mo old and were main- 0.1 mL of ethanol to maintain equal osmotic potential. tained at the USDA-ARS J. Phil Campbell Sr. Natural Mucosal chambers not receiving ergot alkaloids re- Resource Center, Watkinsville, GA in compliance with ceived 0.1 mL of ethanol to maintain uniform test con- animal health and well-being guidelines set by USDA ditions. and the University of Georgia. Ewes grazed bermu- Experiment 1: Ergot Alkaloid Transport in Ruminal dagrass pasture and shade, water, and salt blocks con- and Omasal Tissues. Tissues from two ewes were used taining trace minerals were available at all times. The for this study: each ewe served as a tissue donor on a ewes were killed using a captive bolt before tissues separate day. Four parabiotic chambers were prepared were excised for alkaloid transport analyses. using ruminal posterior ventral sac and tissue from In vitro transport of ergot alkaloids from mucosal omasal plies from each animal. Two chambers for each to serosal sides of the tissues was performed using tissue type were randomly assigned to one of two water parabiotic chambers as described by Matthews and baths. Tissue types within each water bath were ran- Webb (1995). Ruminal, reticular, and omasal compart- domly assigned to alkaloid 180 and 240 min after ad- ments were surgically removed from animals within ministration of the alkaloids to the mucosal chamber 5 min of death. Ruminal, reticular, and omasal com- by aspirating 300 ␮L of solution. Alkaloid appearance partments were emptied of their contents by inverting in the serosal chamber was determined using a com- the chambers, rinsing them clean with tap water, and petitive ELISA procedure as described by Adcock et transporting them to the laboratory in 0.85% saline al. (1997). β-Hydroxybutyric acid was determined en- solution. Tissues were received in the laboratory and zymatically in serosal solutions (Gau, 1987) to verify immediately placed in Kreb’s ringer phosphate (KRP) tissue viability. After the 240-min sample was taken, solution (Umbreit et al., 1964). Ruminal and reticular a 1.5-mL volume of mucosal and serosal buffer was tissues were prepared by removing the musculature aspirated from the chambers and lyophilized. Concen- from the serosal sides of the tissues and placing them trations of ergot alkaloids were determined in the ly- in KRP with 10 mM glucose (KRPG) prior to place- ophilized serosal buffer using HPLC (Rottinghaus et ment in parabiotic chambers. Omasal tissue was pre- al., 1993) to determine tissue transport. pared by peeling plies in half to expose the serosal The remaining tissues from the rumen, reticulum, sides of the tissue before placing it in the KRPG. and omasum were cut into sections and traced on 21.6- A 95:5 mixture of oxygen:carbon dioxide was bub- × 27.9-cm plain white paper. The outlines of the tissue bled through KRPG buffer for 60 min in a water bath were cut and the paper pieces representing the area maintained at 39°C prior to each study. Tissues sec- of each tissue type were dried at 70°C for 16 h in a tions, approximately 2 × 2 cm, were placed into the convection oven and weighed. A 120-cm2 section of parabiotic chambers, rubber O-rings were placed on paper was cut, dried, and weighed to obtain a standard the mucosal side of the tissues, and the chambers were weight per unit area for the paper. The paper pieces sealed with thumb-screw clamps. Each side of the representing the tissues were weighed, and the area chamber was filled with 10 mL of the gassed KRPG of the paper was calculated to estimate the relative buffer and placed in a water bath maintained at 39°C.
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