Yamaji M, Takada M, Fujiwara R, Ohishi H, Izushi K, Sugimoto Y, Kamei C
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Methods Find Exp Clin Pharmacol. 1997 Nov;19(9):637-43.
The role of substance P in experimental allergic conjunctivitis induced by egg albumin was investigated with guinea pigs. Increase in vascular permeability of the conjunctiva induced by antigen was significantly inhibited after repeated application of capsaicin. Substance P contents in the conjunctiva of guinea pig were decreased by topical instillation of antigen to the eyes, suggesting that substance P was released from the conjunctiva due to antigen-antibody reaction. Moreover, subconjunctival injection of substance P resulted in a dose-related conjunctivitis, and vascular permeability in the conjunctiva was also increased by substance P. In substance P-induced conjunctivitis, a significant edema was observed in the bulbar and palpebral conjunctiva, but no hyperemia was noted in all instances. Histamine contents of the conjunctiva and tears were not influenced by subconjunctival injection of substance P. However, topical application of antigen and subconjunctival injection of compound 48/80 caused a significant decrease in histamine content, and content of tear was increased by both treatments. An increase in vascular permeability induced by antigen application was significantly inhibited by intravenous injection of FK-888, which is a specific and potent NK1 receptor antagonist. From these results, it is suggested that substance P is responsible for allergic conjunctivitis to some extent, and the conjunctival hyperpermeability induced by substance P occurs through NK1 receptor on the blood vessels, rather than by the direct action on the conjunctival mast cells during allergic conjunctival reactions.
用豚鼠研究了P物质在卵清蛋白诱导的实验性变应性结膜炎中的作用。反复应用辣椒素后，抗原诱导的结膜血管通透性增加受到显著抑制。向豚鼠眼局部滴注抗原后，结膜中P物质含量降低，提示P物质因抗原-抗体反应从结膜释放。此外，结膜下注射P物质导致剂量相关的结膜炎，P物质也增加了结膜的血管通透性。在P物质诱导的结膜炎中，可见球结膜和睑结膜明显水肿，但并非所有病例均有充血。结膜下注射P物质对结膜和泪液中的组胺含量无影响。然而，局部应用抗原和结膜下注射48/80化合物导致组胺含量显著降低，两种处理均使泪液含量增加。静脉注射特异性强效NK1受体拮抗剂FK-888可显著抑制抗原应用诱导的血管通透性增加。从这些结果提示，P物质在一定程度上参与变应性结膜炎的发生，P物质诱导的结膜高通透性是通过血管上的NK1受体发生的，而不是变应性结膜反应期间对结膜肥大细胞的直接作用。
