Adrenomedullin regulates blood-brain barrier functions in vitro.
Adrenomedullin (AM) is an important vasodilator in cerebral circulation, and cerebral endothelial cells are a major source of AM. This in vitro study aimed to determine the AM-induced changes in blood-brain barrier (BBB) functions. AM administration increased, whereas AM antisense oligonucleotide treatment decreased transendothelial electrical resistance. AM incubation decreased BBB permeability for sodium fluorescein (mol. wt 376 Da) but not for Evan's blue albumin (mol. wt 67 kDa), and it also attenuated fluid-phase endocytosis. AM treatment resulted in functional activation of P-glycoprotein efflux pump in vitro. Our results indicate that AM as an autocrine mediator plays an important role in the regulation of BBB properties of the cerebral endothelial cells.
Kis
B
B
Department of Physiology, University of Occupational and Environmental Health, Iseigaoka 1-1 Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Deli
M A
MA
Kobayashi
H
H
Abrahám
C S
CS
Yanagita
T
T
Kaiya
H
H
Isse
T
T
Nishi
R
R
Gotoh
S
S
Kangawa
K
K
Wada
A
A
Greenwood
J
J
Niwa
M
M
Yamashita
H
H
Ueta
Y
Y
D053607:Adrenomedullin; D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D004396:Coloring Agents / Q000493:pharmacokinetics; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005070:Evans Blue / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020112:Rhodamine 123 / Q000493:pharmacokinetics; D014665:Vasodilator Agents / Q000494:pharmacology*
D000418:Albumins; D004396:Coloring Agents; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D010455:Peptides; D014665:Vasodilator Agents; C104782:adrenomedullin (22-52); D053607:Adrenomedullin; D020112:Rhodamine 123; D005070:Evans Blue