title: Actions of tachykinins on the rabbit mesenteric artery: substance P and [Glp6,L-Pro9]SP6-11 are potent agonists for endothelial neurokinin-1 receptors.
abstract: 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.
authors: Department of Anatomy, University College, London.
authors: A
authors: A
authors: Stewart-Lee
authors: G
authors: G
authors: Burnstock
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*; D015320:Tachykinins / Q000494:pharmacology*; D014665:Vasodilator Agents
chemical_list: D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; D014665:Vasodilator Agents; D013373:Substance P; D009638:Norepinephrine