Edvinsson L, Jansen I
Br J Pharmacol. 1987 Mar;90(3):553-9. doi: 10.1111/j.1476-5381.1987.tb11205.x.
In circular lengths cut from the basilar artery of guinea-pig (0.2-0.3 mm o.d.) relaxations induced by substance P and neurokinin A were highly susceptible to mechanical damage of the endothelium by rubbing. The precontraction induced by prostaglandin F2 alpha but not that of 124 mM potassium was reduced considerably by the rubbing procedure. Concentration-dependent relaxations were evoked by tachykinin agonists in the following order of potency: substance P = physalaemin greater than neurokinin A greater than eledoisin. Physalaemin was, however, a partial agonist, giving only half the maximum relaxation as compared to the other tachykinins. The two putative tachykinin receptor antagonists, spantide ([D-Arg1, D-Trp7,9, D-Leu11] substance P) and [D-Pro2, D-Trp7,9] substance P, shifted the concentration-dependent relaxations of substance P to the right in a parallel manner. Calculation of pA2 values and Schild plot analysis revealed pA2 values of 7.4-7.6 for spantide and 6.9-7.0 for [D-Pro2, D-Trp7,9] substance P, irrespective of whether substance P or neurokinin A was used as agonist. The pA2 values and the Schild plot analysis suggest a specific interaction between tachykinin agonists and antagonists that follow a simple bimolecular process. The results suggest the presence of tachykinin receptors of the 'SP-P' type in guinea-pig basilar arteries which, for induction of relaxation, involves the release of an endothelium-derived relaxing factor.
从豚鼠基底动脉切下的环状血管段（外径0.2 - 0.3毫米），P物质和神经激肽A诱导的舒张对通过摩擦造成的内皮机械损伤高度敏感。前列腺素F2α诱导的预收缩，但124 mM钾诱导的预收缩不受摩擦操作的显著影响。速激肽激动剂诱发浓度依赖性舒张的效力顺序如下：P物质 = 雨蛙肽＞神经激肽A＞eledoisin。然而，雨蛙肽是一种部分激动剂，与其他速激肽相比，其最大舒张仅为一半。两种假定的速激肽受体拮抗剂，spantide（[D - Arg1, D - Trp7,9, D - Leu11]P物质）和[D - Pro2, D - Trp7,9]P物质，以平行方式将P物质的浓度依赖性舒张向右移动。计算pA2值并进行Schild图分析显示，无论使用P物质还是神经激肽A作为激动剂，spantide的pA2值为7.4 - 7.6，[D - Pro2, D - Trp7,9]P物质的pA2值为6.9 - 7.0。pA2值和Schild图分析表明速激肽激动剂和拮抗剂之间存在遵循简单双分子过程的特异性相互作用。结果表明豚鼠基底动脉中存在“SP - P”型速激肽受体，其舒张诱导涉及内皮源性舒张因子的释放。
