Endothelium-dependent contraction in intrapulmonary arteries: mediation by endothelial NK1 receptors and TXA2.
1. We have examined whether three natural tachykinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) induce an endothelium-dependent contraction (EDC) in the rabbit isolated intrapulmonary artery. 2. Removal of the endothelium almost abolished the contraction induced by SP (10(-8) M) while it did not attenuate the contraction induced by SP (10(-7) M), NKA (10(-9) - 10(-7) M) or NKB (10(-8) and 10(-7) M). 3. The EDC induced by SP (10(-8) M) was abolished by NK1 antagonists (FK-888, CP-96345, CP-99994 and SR-140333) but not by an NK2 antagonist (SR-48968). 4. The EDC induced by SP was attenuated by cyclo-oxygenase inhibitors (aspirin and indomethacin), thromboxane A2 (TXA2) synthetase inhibitors (OKY-046, KY-234 and KY-063) and a TXA2 antagonist (S-1452). 5. The rank order of potency causing endothelium-independent contraction (EIC) was NKA > NKB > SP. The EIC induced by SP (10(-7) M) was attenuated by an NK2 antagonist but not by NK1 antagonists, cyclo-oxygenase inhibitors, TXA2 synthetase inhibitors or a TXA2 antagonist. 6. In conclusion, SP at 10(-8) M induces EDC via endothelial NK1 receptors and TXA2 production, and SP at 10(-7) M induces EIC via NK2 receptors in the rabbit intrapulmonary artery.
Shirahase
H
H
Pharmacology Division, Kyoto University, Japan.
Kanda
M
M
Kurahashi
K
K
Nakamura
S
S
Usui
H
H
Shimizu
Y
Y
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D011817:Rabbits; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D016861:Cyclooxygenase Inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; D013373:Substance P; D013928:Thromboxane A2; D015288:Neurokinin A; D015287:Neurokinin B; D013930:Thromboxane-A Synthase