title: Chronic adrenomedullin treatment improves blood-brain barrier function but has no effects on expression of tight junction proteins.
abstract: We previously found that the production of adrenomedullin (AM) is one magnitude higher in cerebral endothelial cells (CECs) than in the peripheral endothelium and the AM concentration in the cerebral circulation is significantly higher than in other tested parts of the circulation. We also showed that CECs express AM receptors, and AM as an autocrine hormone is important to regulate the intracellular cAMP level in CECs. Further we reported that acute AM treatment has cAMP-like effects on specific BBB functions: AM decreased endothelial fluid phase endocytosis, activated the P-glycoprotein, increased transendothelial electrical resistance (TEER) and reduced endothelial permeability for sodium fluorescein, which suggests a tightening of intercellular junctions. In the present study, we found chronic AM exposure also increased TEER. In contrast, we could not detect significant effect of AM on the expression of tight junction proteins (claudin-1, occludin and zonula occludens-1). While not affecting expression of tight junction proteins, chronic AM treatment may influence the localization of these proteins which has been reported to correlate with functional changes of the BBB without a change in protein expression.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Winston-Salem, NC 27157, USA. bkis@wfubmc.edu
authors.forename: B
authors.initials: B
authors.lastname: Kis
authors.forename: J A
authors.initials: JA
authors.lastname: Snipes
authors.forename: M A
authors.initials: MA
authors.lastname: Deli
authors.forename: C S
authors.initials: CS
authors.lastname: Abrahám
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
authors.forename: Y
authors.initials: Y
authors.lastname: Ueta
authors.forename: D W
authors.initials: DW
authors.lastname: Busija
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D062445:Claudin-1; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D062793:Occludin; D010455:Peptides / Q000008:administration & dosage*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
chemical_list: D062445:Claudin-1; C568114:Cldn1 protein, rat; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010455:Peptides; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D053607:Adrenomedullin