Qian Y, Emonds-Alt X, Advenier C
Laboratoire de Pharmacologie, Faculté de Médecine Paris-Ouest, France.
Pulm Pharmacol. 1993 Mar;6(1):63-7. doi: 10.1006/pulp.1993.1009.
The aim of this study was to demonstrate the involvement of neuropeptides in the increase in microvascular permeability induced by bradykinin in guinea-pig airways in vivo and to determine the type of receptor involved. Extravasation of intravenously injected Evans blue dye was used as an index of vascular permeability. Increase in plasma exudation induced by bradykinin (0.3 micrograms/kg, iv) was reduced or abolished by capsaicin (40 mg/kg, sc, 7 days before experiments), a drug which destroys neurokinins in the NANC nerve endings. (+/-)-CP-96,345 (3 mg/kg, iv), an antagonist of neurokinin NK1-receptors, abolished the increase of vascular permeability induced by bradykinin and reduced or abolished the effects of substance P (0.3 micrograms/kg, iv). The higher dose of (+/-)-CP-96,345 (10 mg/kg, iv) completely blocked the effects of substance P, but it did not modify those of neurokinin A (100 micrograms/kg, iv). In contrast, SR 48968 (0.1 and 0.3 mg/kg, iv), an antagonist of neurokinin NK2-receptors, reduced the increase of vascular permeability induced by neurokinin A without influencing the effects of bradykinin and substance P. These results demonstrate that a stimulation of the non-adrenergic non-cholinergic (NANC) nerves and a subsequent release of neuropeptides, especially of substance P, is involved in the effects of bradykinin.
本研究的目的是证明神经肽在豚鼠气道体内缓激肽诱导的微血管通透性增加中的作用，并确定所涉及的受体类型。静脉注射伊文思蓝染料的外渗用作血管通透性的指标。辣椒素（40mg/kg，皮下注射，实验前7天）可减少或消除缓激肽（0.3μg/kg，静脉注射）诱导的血浆渗出增加，辣椒素是一种可破坏非肾上腺素能非胆碱能（NANC）神经末梢中神经激肽的药物。（±）-CP-96,345（3mg/kg，静脉注射），一种神经激肽NK1受体拮抗剂，可消除缓激肽诱导的血管通透性增加，并减少或消除P物质（0.3μg/kg，静脉注射）的作用。较高剂量的（±）-CP-96,345（10mg/kg，静脉注射）完全阻断了P物质的作用，但未改变神经激肽A（100μg/kg，静脉注射）的作用。相反，神经激肽NK2受体拮抗剂SR 48968（0.1和0.3mg/kg，静脉注射）可减少神经激肽A诱导的血管通透性增加，而不影响缓激肽和P物质的作用。这些结果表明，非肾上腺素能非胆碱能（NANC）神经的刺激以及随后神经肽尤其是P物质的释放参与了缓激肽的作用。
