[Tachykinin receptor subtypes involved in endothelium-dependent and -independent responses in rabbit intrapulmonary arteries].
In the present study, it was demonstrated that SP, neurokinin A (NKA), neurokinin B (NKB), SP methyl ester (SPME), [Ala5, beta-Ala8]-alpha-neurokinin fragment 4-10 (AANF) at 10(-8) M all caused contraction in non-contracted endothelium-intact arteries. SP- and SPME-induced contraction were reduced by removal of endothelium. All the peptides with the exception of AANF induced transient relaxation in the precontracted arteries. The relaxation were attenuated by removal of endothelium. The potency orders for endothelium-dependent contraction (EDC), -dependent relaxation (EDR) and -independent contraction (EIC) were SP > SPME >> NKA [symbol: see text] NKB [symbol: see text] AANF, SP > SPME > NKA > NKB >> AANF and NKA > AANF > NKB >> SP [symbol: see text] SPME, respectively. SP-induced EDC and EDR were attenuated by an NK1 antagonist but not by an NK2 antagonist. The SP-induced EIC was reduced by an NK2 antagonist. SP-induced EDC was attenuated by aspirin, OKY-046, and S-1452. The EDR was attenuated by L-NAME and methylene blue. The EDC induced by SPME was non-competitively attenuated by CP-99994, an NK1 antagonist. EDR was competitively inhibited by CP-99994. In conclusion, SP and related peptides caused EDC via NK1 receptors and TXA2 production, EDR via NK1 receptors and NO release and EIC via NK2 receptors in rabbit intrapulmonary arteries.
Shirahase
H
H
Division of Pharmacology, RI Center, Kyoto University, Japan.
Kanda
M
M
Murase
K
K
Nakamura
S
S
Jino
H
H
Usui
H
H
Kurahashi
K
K
D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D011817:Rabbits; D018039:Receptors, Tachykinin / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018039:Receptors, Tachykinin; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; C033611:substance P, methyl ester-; D015288:Neurokinin A; D015287:Neurokinin B