Jacoby H I, Lopez I, Wright D, Vaught J L
Life Sci. 1986 Nov 24;39(21):1995-2003. doi: 10.1016/0024-3205(86)90323-1.
We have studied the selectivity and competitiveness of three neurokinin antagonists and atropine against substance P, neurokinin A, and neurokinin B. DPDTNLE-NB, [D-Pro2, D-Trp6,8, Nle10]-neurokinin B is a competitive antagonist of neurokinin B (pA2 = 5.5), but not substance P or neurokinin A. DPDT-SP ([D-Pro2,Trp7,9]-substance P), competitively blocks substance P (pA2 = 6.9) and neurokinin B (pA2 = 6.8), but not neurokinin A. Spantide ([D-Arg1, D-Trp7,9, Leu11]-substance P) competitively blocks substance P (pA2 = 6.7) and at a log unit higher concentration blocks neurokinin A (pA2 = 5.8), but does not block neurokinin B. Atropine is a competitive antagonist of neurokinin B (pA2 = 9.0) at ten times the concentration needed to block acetylcholine (pA2 = 10.1), but does not inhibit the other neurokinins. These results support the hypothesis of multiple neurokinin receptors in the guinea pig ileum and indicate that the site of neurokinin B, but not substance P or neurokinin A is predominantly on intramural neurons. This indirect stimulation appears to be dependent on the release of acetylcholine. Neurokinin B also has activity on smooth muscle receptors since the contractile response could not be completely antagonized by atropine. There appear to be two smooth muscle neurokinin receptors on the basis of results obtained with DPDT-SP and spantide, one predominantly responsive to substance P and the other to neurokinin A. Only spantide appeared to have any effect on the neurokinin A receptor and that was at a much higher concentration than that needed to block substance P.
我们研究了三种神经激肽拮抗剂和阿托品对P物质、神经激肽A和神经激肽B的选择性和竞争性。DPDTNLE-NB，[D-脯氨酸2，D-色氨酸6,8，Nle10]-神经激肽B是神经激肽B的竞争性拮抗剂（pA2 = 5.5），但对P物质或神经激肽A无作用。DPDT-SP（[D-脯氨酸2，色氨酸7,9]-P物质）竞争性阻断P物质（pA2 = 6.9）和神经激肽B（pA2 = 6.8），但对神经激肽A无作用。Spantide（[D-精氨酸1，D-色氨酸7,9，亮氨酸11]-P物质）竞争性阻断P物质（pA2 = 6.7），在高一个对数单位浓度时阻断神经激肽A（pA2 = 5.8），但不阻断神经激肽B。阿托品是神经激肽B的竞争性拮抗剂（pA2 = 9.0），其浓度是阻断乙酰胆碱所需浓度的十倍（pA2 = 10.1），但不抑制其他神经激肽。这些结果支持豚鼠回肠中存在多种神经激肽受体的假说，并表明神经激肽B而非P物质或神经激肽A的作用位点主要在壁内神经元上。这种间接刺激似乎依赖于乙酰胆碱的释放。神经激肽B对平滑肌受体也有活性，因为阿托品不能完全拮抗收缩反应。根据用DPDT-SP和Spantide得到的结果，平滑肌上似乎存在两种神经激肽受体，一种主要对P物质有反应，另一种对神经激肽A有反应。只有Spantide似乎对神经激肽A受体有任何作用，且所需浓度远高于阻断P物质所需浓度。
