Neuropeptide Y enhances permeability across a rat aortic endothelial cell monolayer.
Previously, in vivo studies showed that neuropeptide Y (NPY) elevates vascular permeability in isolated lung perfusion preparations, possibly through binding to the NPY Y(3) receptor. The present study used monolayers in a double-chamber culture method under conditions of normoxia (5% CO(2)-20% O(2)-75% N(2)) or hypoxia (5% CO(2)-5% O(2)-90% N(2)) to test the hypothesis that NPY directly affects rat aortic endothelial cells (RAECs). RAECs were cultured on the base of the upper chamber, into which FITC-labeled albumin was introduced, and permeation into the lower chamber was measured. The RAEC monolayer was treated with 10(-8)-3 x 10(-7) M NPY for 2 h in normoxia or hypoxia. In hypoxia, NPY concentration dependently increased the permeability of the RAEC monolayer, whereas in normoxia no significant change was observed. Peptide YY, NPY Y(1), and NPY Y(2) receptor agonists and NPY Y(1) receptor antagonist exerted no significant effects under hypoxic conditions. NPY-(18-36), an NPY Y(3) receptor antagonist, elicited an inhibitory action on the NPY-induced increase in monolayer permeability. Furthermore, neither N-monomethyl-l-arginine, a nitric oxide synthase inhibitor, the bradykinin B(2) receptor antagonist FK-3657, nor the vascular endothelial growth factor receptor-coupled tyrosine kinase inhibitor tyrphostin SU-1498, injected into the medium of the upper chamber, affected the NPY-induced permeability changes under hypoxic conditions. The results suggest that the NPY-induced increase in permeability across the RAEC monolayer is closely related to low O(2) tension, possibly mediated by direct action on the NPY Y(3) receptor expressed on the endothelial cell membrane. Furthermore, this NPY-induced increase is not likely due to nitric oxide, bradykinin, or vascular endothelial growth factor.
Dept. of Pharmacology, Aichi Medical Univ., School of Medicine, Nagakute, Aichi 480-1195, Japan. nao@aichi-med-u.ac.jp
Yong-Shan
YS
Nan
Guo-Gang
GG
Feng
Yoshihiro
Y
Hotta
Kimitoshi
K
Nishiwaki
Yasuhiro
Y
Shimada
Atsuko
A
Ishikawa
Nakako
N
Kurimoto
Tatsuro
T
Shigei
Naohisa
N
Ishikawa
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D019894:Peptide YY / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000819:agonists; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D014151:Anti-Anxiety Agents; C092926:BIBP 3226; D065094:Bradykinin B2 Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; D042461:Vascular Endothelial Growth Factor A; D019894:Peptide YY; C059889:neuropeptide Y (18-36); D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D006632:Histamine; D001120:Arginine; D000242:Cyclic AMP; D040262:Receptors, Vascular Endothelial Growth Factor; D001920:Bradykinin; D007213:Indomethacin