Actions of tachykinins on the rabbit mesenteric artery: Substance P and [Glp⁶,L-Pro⁹]SP_6-11 are potent agonists for endothelial neurokinin-1 receptors

TY - JOUR

T1 - Actions of tachykinins on the rabbit mesenteric artery

T2 - Substance P and [Glp6,L-Pro9]SP6-11 are potent agonists for endothelial neurokinin-1 receptors

AU - Stewart-Lee, A.

AU - Burnstock, G.

PY - 1989/8

Y1 - 1989/8

N2 - 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 μM, with a rank order of potency substance P > neurokinin A > neurokinin B. 5. At a concentration of 0.1 μM, 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.

AB - 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 μM, with a rank order of potency substance P > neurokinin A > neurokinin B. 5. At a concentration of 0.1 μM, 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.

U2 - 10.1111/j.1476-5381.1989.tb12581.x

DO - 10.1111/j.1476-5381.1989.tb12581.x

M3 - Article

C2 - 2477103

AN - SCOPUS:0024805199

SN - 0007-1188

VL - 97

SP - 1218

EP - 1224

JO - British journal of pharmacology

JF - British journal of pharmacology

IS - 4

ER -