Tachykinin NK1 receptor-mediated vasorelaxation in human pulmonary arteries.
Tachykinin NK1 receptors are present on human pulmonary arteries. Addition of the specific tachykinin NK1 receptor agonist, [Met-OMe11]substance P produced a concentration-dependent relaxation (0.1 nM to 100 nM) in pulmonary arteries preconstricted with phenylephrine (30 microM). The EC50 (agonist concentration needed to produce 50% of the maximal relaxation) value for [Met-OMe11]substance P was 3.7+/-0.7 nM. The relaxation induced by [Met-OMe11]substance P was selectively inhibited by the tachykinin NK1 receptor antagonist CP 99994 (1 nM), with a pKb of 9.9+/-0.3. Treatment with the tachykinin NK2 receptor antagonist SR 48968 (100 nM) did not significantly affect the vasorelaxation due to [Met-OMe11]substance P (P > 0.05, one-way analysis of variance; ANOVA).
Corboz
M R
MR
Allergy, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. michel.corboz@spcorp.com
Rivelli
M A
MA
Ramos
S I
SI
Rizzo
C A
CA
Hey
J A
JA
D004305:Dose-Response Relationship, Drug; D006801:Humans; D010656:Phenylephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D010880:Piperidines; D018040:Receptors, Neurokinin-1; D014662:Vasoconstrictor Agents; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D010656:Phenylephrine; D013373:Substance P