Hamel R, Ford-Hutchinson A W, Blazejczak C, Van den Brekel A
Department of Pharmacology, Merck Frosst Canada Inc., Pointe-Claire-Dorval, Qué.
Can J Physiol Pharmacol. 1988 Nov;66(11):1361-7. doi: 10.1139/y88-223.
Permeability changes in the guinea-pig skin following intradermal (i.d.) injection of tachykinin agonists or antigen were monitored through the extravasation of 99mTc-labelled human serum albumin and blood flow changes through the accumulation of 51Cr-labelled microspheres. A variety of synthetic and natural tachykinins, including substance P and neurokinins A and B, were shown to be potent inducers of permeability changes. Neurokinins A and B, but not substance P, were also shown to be apparent vasoconstrictor agents. Permeability responses in sensitized guinea pigs to i.d. injection of antigen and substance P, but not histamine, were abolished by pretreatment with the tachykinin antagonists [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P and [D-Pro2, D-Trp7,9]-substance P. Interpretation of such results was complicated by the fact that such antagonists may in themselves induce mast cell activation. Depletion of substance P containing neurons by pretreatment of guinea pigs with capsaicin also produced significant inhibition of antigen-induced permeability changes. These results indicate a possible role for tachykinins, such as substance P, in cutaneous anaphylaxis in the guinea pig.
通过99mTc标记的人血清白蛋白外渗监测豚鼠皮内（i.d.）注射速激肽激动剂或抗原后皮肤的通透性变化，并通过51Cr标记的微球积累监测血流变化。包括P物质以及神经激肽A和B在内的多种合成和天然速激肽被证明是通透性变化的有效诱导剂。神经激肽A和B，但不是P物质，也被证明是明显的血管收缩剂。速激肽拮抗剂[D-Arg1，D-Pro2，D-Trp7,9，Leu11]-P物质和[D-Pro2，D-Trp7,9]-P物质预处理可消除致敏豚鼠对i.d.注射抗原和P物质（而非组胺）的通透性反应。由于这些拮抗剂本身可能诱导肥大细胞活化，使得对此类结果的解释变得复杂。用辣椒素预处理豚鼠以耗尽含P物质的神经元，也可显著抑制抗原诱导的通透性变化。这些结果表明速激肽如P物质在豚鼠皮肤过敏反应中可能起作用。
