Actions of tachykinins on the rabbit mesenteric artery: substance P and [Glp6,L-Pro9]SP6-11 are potent agonists for endothelial neurokinin-1 receptors.

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 [Glp6,L-Pro9]SP6-11 (L-Pro), [Glp6,D-Pro9]SP6-11 (D-Pro) and N-succinyl-[Asp6,MePhe8]SP6-11 (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 microM, with a rank order of potency substance P greater than neurokinin A greater than neurokinin B. 5. At a concentration of 0.1 microM, 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.