Potentiation by neuropeptide Y of 5HT2A receptor-mediated contraction in porcine coronary artery.
Potentiation by neuropeptide Y of serotonin (5-HT)-induced vasoconstriction was investigated in porcine coronary artery. 5-HT caused concentration-dependent contraction through 5-HT2A receptors. Neuropeptide Y (30 nM) significantly increased the 5HT-induced contraction by 16+/-5% in arteries with intact endothelium. Removal of the endothelium abolished the potentiation. A neuropeptide Y1 antagonist, BIBP3226, blocked this neuropeptide Y-induced potentiation. In vessels with intact endothelium, the potentiation by neuropeptide Y was inhibited by in the presence of a cyclo-oxygenase inhibitor, indomethacin (30 microM), but not by the presence of ETA or ETB endothelin receptor antagonists or an NO synthase inhibitor, NG-nitro-L-arginine (L-NNA) (1 mM) at all. A thromboxane A2 (TXA2) synthase inhibitor, ozagrel, and prostanoid TP receptor antagonists, seratrodast and ONO-3708, also inhibited the neuropeptide Y-induced potentiation. In the endothelium-denuded arteries, a prostanoid TP receptor agonist, U-46619 (0.01-0.1 nM), potentiated 5-HT-induced contraction. These results indicate that neuropeptide Y potentiates the 5-HT-induced contraction, due to release of TXA2 from the endothelium via neuropeptide Y1 receptors, in porcine coronary artery.
Tsurumaki
Tatsuru
T
Division of Pharmacology, Department of Molecular Genetics and Signal Transduction Research, Course for Molecular and Cellular Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.
Nagai
Shingo
S
Bo
Xu
X
Toyosato
Akira
A
Higuchi
Hiroshi
H
D000818:Animals; D003331:Coronary Vessels / Q000473:pathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009478:Neuropeptide Y / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D017466:Receptors, Endothelin / Q000378:metabolism; D013552:Swine; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D016861:Cyclooxygenase Inhibitors; D009478:Neuropeptide Y; D044402:Receptor, Serotonin, 5-HT2A; D017466:Receptors, Endothelin; D019335:Nitroarginine; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase