title: Corticotropin-releasing factor (CRF) can directly affect brain microvessel endothelial cells.
abstract: Stress activates the hypothalamic-pituitary-adrenal (HPA) axis through release of corticotropin releasing factor (CRF), leading to production of glucocorticoids that down regulate immune responses. However, acute stress via CRF also has pro-inflammatory effects. We previously showed that acute stress increases rat blood-brain barrier (BBB) permeability, an effect involving brain mast cells and CRF, as it was absent in W/W(v) mast cell-deficient mice and was blocked by the CRF-receptor antagonist, Antalarmin. We investigated if CRF could also have a direct action on brain microvessel endothelial cells (BMEC) isolated from rat and bovine brain. BMEC were cultured and identified by electron microscopy. Western blot analysis of cultured BMEC identified CRF receptor protein; stimulation with CRF, or it structural analogue urocortin (Ucn) showed that the receptor is functionally coupled to adenylate cyclase as it increased cyclic AMP (cAMP) levels by 2-fold. These findings suggest that CRF could affect BMEC structure or function, as reported for increased cAMP levels by other studies. It is, therefore, possible that CRF may directly regulate BBB permeability, in addition to any effect mediated via brain mast cells.
authors.affiliation: Department of Pharmacology, Tufts University School of Medicine, New England Medical Center, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Esposito
authors.forename: Subimal
authors.initials: S
authors.lastname: Basu
authors.forename: Richard
authors.initials: R
authors.lastname: Letourneau
authors.forename: Stanley
authors.initials: S
authors.lastname: Jacobson
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000033:anatomy & histology / Q000166:cytology* / Q000648:ultrastructure; D002417:Cattle; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000145:classification / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution; D014463:Ultrasonography; D054832:Urocortins
chemical_list: D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP