title: Permeability of ergot alkaloids across the blood-brain barrier in vitro and influence on the barrier integrity.
abstract: METHODS
  Ergot alkaloids are secondary metabolites of Claviceps spp. and they have been in the focus of research for many years. Experiments focusing on ergotamine as a former migraine drug referring to the ability to reach the brain revealed controversial results. The question to which extent ergot alkaloids are able to cross the blood-brain barrier is still not answered.
  
  
  RESULTS
  In order to answer this question we have studied the ability of ergot alkaloids to penetrate the blood-brain barrier in a well established in vitro model system using primary porcine brain endothelial cells. It could clearly be demonstrated that ergot alkaloids are able to cross the blood-brain barrier in high quantities in only a few hours. We could further identify an active transport for ergometrine as a substrate for the BCRP/ABCG2 transporter. Investigations concerning barrier integrity properties have identified ergocristinine as a potent substance to accumulate in these cells ultimately leading to a weakened barrier function.
  
  
  CONCLUSIONS
  For the first time we could show that the so far as biologically inactive described 8-(S) isomers of ergot alkaloids seem to have an influence on barrier integrity underlining the necessity for a risk assessment of ergot alkaloids in food and feed.
authors.affiliation: NRW Graduate School of Chemistry University of Münster, Münster, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Mulac
authors.forename: Sabine
authors.initials: S
authors.lastname: Hüwel
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Galla
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004873:Ergolines / Q000493:pharmacokinetics*; D004874:Ergonovine / Q000493:pharmacokinetics*; D004878:Ergotamine / Q000493:pharmacokinetics*; D007536:Isomerism; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D010539:Permeability; D013395:Sucrose / Q000493:pharmacokinetics; D013552:Swine
chemical_list: D004873:Ergolines; C100270:ergocristine; D013395:Sucrose; D004878:Ergotamine; D004874:Ergonovine