Neuropeptide Y reduces macromolecule permeability of coronary endothelial monolayers.
The effect of neuropeptide Y (NPY) on cellular adenosine 3',5'-cyclic monophosphate (cAMP) contents and macromolecule permeability was studied in cultured monolayers of microvascular coronary endothelial cells from rat. Macromolecule permeability was continuously determined as passage of albumin across the monolayers. NPY (10(-10)-10(-7) M) decreased albumin flux and cellular cAMP content in a dose-dependent manner, with a half-maximal effect on albumin flux at 1.4 x 10(-9) M and on cAMP contents at 0.7 x 10(-9) M. A maximum effect of NPY was observed at 10(-7) M, decreasing albumin flux by 71 +/- 8% and cellular cAMP contents by 80 +/- 9% (mean +/- SD, n = 6, P < 0.05) compared with control. The effect of NPY on albumin flux was not altered in the presence of 10(-5) M indomethacin (an inhibitor of cyclooxygenase) and 10(-5) M NG-nitro-L-arginine (an inhibitor of nitric oxide synthase). NPY (10(-7) M) also antagonized the increase of albumin flux and cAMP content induced by 10(-6) M isoproterenol. Pretreatment of endothelial monolayers with pertussis toxin (1 microgram/ml for 2 h) abolished the effect of NPY on albumin flux and cAMP contents. This study shows that NPY can modulate macromolecule permeability of endothelial monolayers by reducing the cellular cAMP contents. Together with the effect of pertussis toxin, the data suggest that NPY exerts its antiadrenergic effect on cAMP metabolism and endothelial barrier function by receptors linked to adenylyl cyclase via an inhibitory guanosine-binding protein in coronary endothelial cells.
Noll
T
T
Physiologisches Institut, Justus-Liebig-Universität, Giessen, Germany.
Hempel
A
A
Piper
H M
HM
D037361:Adenylate Cyclase Toxin; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D046911:Macromolecular Substances; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D004791:Enzyme Inhibitors; D046911:Macromolecular Substances; D009478:Neuropeptide Y; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D019335:Nitroarginine; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D007545:Isoproterenol