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Actions of tachykinins on the rabbit mesenteric artery: substance P and [Glp 6 ,L‐Pro 9 ]SP 6–11 are potent agonists for endothelial neurokinin‐1 receptors
Author(s) -
StewartLee Anne,
Burnstock Geoffrey
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb12581.x
Subject(s) - neurokinin a , neurokinin b , substance p , tachykinin receptor , endocrinology , medicine , endothelium , receptor , tachykinin receptor 1 , chemistry , biology , neuropeptide
1 Identification of the subtype of neurokinin receptor on the endothelium of the rabbit mesenteric artery was demonstrated by comparing the relative potencies of the naturally occurring tachykinins, substance P, neurokinin A and neurokinin B and the highly selective agonists [Glp 6 ,L‐Pro 9 ]SP 6–11 (L‐Pro), [Glp 6 ,D‐Pro 9 ]SP 6–11 (D‐Pro) and N‐succinyl‐[Asp 6 ,MePhe 8 ]SP 6–11 (senktide). 2 Relaxations of the rabbit mesenteric artery to substance P, neurokinin A and neurokinin B were concentration‐dependent and were abolished by the removal of the endothelium. 3 Substance P was more potent than neurokinin A or neurokinin B and L‐Pro was more potent than D‐Pro or senktide. 4 Substance P, neurokinin A and neurokinin B all significantly reduced the nerve‐mediated contractile response in the presence of the endothelium at a concentration of 0.1 μ m , with a rank order of potency substance P > neurokinin A > neurokinin B. 5 At a concentration of 0.1 μ m , L‐Pro also significantly reduced the nerve‐mediated contractile response, unlike D‐Pro and senktide. 6 It is concluded that the relaxation of the rabbit mesenteric artery produced by substance P is mediated by neurokinin‐1 receptors (NK‐1) located on the endothelium. Furthermore, of the analogues, L‐Pro was particularly potent for these receptors.