ERGOVALINE MOVEMENT ACROSS CACO-2 CELLS

Abstract

Ergovaline's role in the direct causation of fescue toxicosis first requires establishment of its dietary absorption. Therefore, ergovaline movement across human intestinal cells was assessed using Caco-2 cells derived from human colon carcinoma. A pre-equilibrated mixture of ergovaline/ergovalinine (60:40 ratio of isomers) was added to the apical compartment, and isomer movements were assessed by high-performance liquid chromatography (HPLC) of extracted media (initial pre-isomerized ergovaline concentrations of 6 and 22 microM, two doses). Mathematical models for ergot alkaloid movement were developed. Rates of movement were not different for the isomers. In the absence of cells, basal accumulation of isomers was essentially linear for 3 h regardless of loading concentration, after which basal accumulation of ergovaline/ergovalinine plateaued. Rates of ergovaline/ergovalinine movement in the presence of cells slowed to about 25% the rate of movement in the absence of cells (22 microM, kt = 0.0133 no cells, 0.0036 with cells, P < 0.05). Mass transfer rate was 7.5 ng x cm(-2) x min(-1) and was similar to that reported for ergovaline using a parabiotic chamber with sheep omasum. After 6 h in the presence of cells, approximately 25 and 40% of the total ergovaline/ergovalinine administered had accumulated in the basal compartment for 6.6 and 22 microM treatments, respectively. Ergovaline and its naturally occurring isomer, ergovalinine, readily crossed intestinal cells intact and at similar rates. Either isomer, or a combination of both, could be involved in the pathogenesis of fescue toxicosis at sites distal to the intestine.