Marceau F, Hugli T E
J Pharmacol Exp Ther. 1984 Sep;230(3):749-54.
Four major guinea-pig blood vessels were isolated and studied in vitro for their contractile responses to anaphylatoxins C3a and C5a. Both peptides were assayed in the 10(-9) to 10(-7) M range and their effects were parallel, although C3a was less potent and more tachyphylactic than C5a. The most responsive blood vessel, relative to a histamine maximal response, was the portal vein, followed by the pulmonary artery and the thoracic aorta. The abdominal vena cava did not respond to either C3a or C5a. Participation of secondary mediators in the vasoconstrictor effect of C3a and C5a was assessed by exposing portal veins and pulmonary arteries to specific inhibitors. The four drugs were: indomethacin, a cyclooxygenase inhibitor; pyrilamine, an antagonist of H1 receptors for histamine; FPL55712, an antagonist of the leukotriene component of slow-reacting substance of anaphylaxis; and phentolamine, an alpha adrenergic blocker. This pharmacological analysis suggests that prostaglandin-like substances mediate most of the anaphylatoxin vasoconstrictor effects, with a biologically significant participation of leukotrienes in the case of C3a and histamine in the case of C5a. High variability between individual tissue responses to the anaphylatoxins was investigated in terms of previous exposure to activated complement. Cobra venom factor (200 micrograms) was injected i.v. in five guinea pigs 2 hr before sacrifice. This treatment reduced the serum concentration of C3 and C5 to 9 and 32%, respectively, as compared with saline-treated animals. The portal vein excised from the cobra venom factor-treated animals exhibited reduced sensitivities to C3a, but showed normal response to C5a. The selective desensitization to C3a after complement activation in vivo is presumably related to the highly tachyphylactic effect of C3a on blood vessels.
分离出豚鼠的四条主要血管，在体外研究它们对过敏毒素C3a和C5a的收缩反应。两种肽的浓度范围为10⁻⁹至10⁻⁷M，它们的作用是平行的，尽管C3a的效力低于C5a，且更易产生快速耐受性。相对于组胺最大反应，反应最敏感的血管是门静脉，其次是肺动脉和胸主动脉。腹静脉对C3a和C5a均无反应。通过将门静脉和肺动脉暴露于特定抑制剂来评估二级介质在C3a和C5a血管收缩作用中的参与情况。这四种药物分别是：吲哚美辛，一种环氧化酶抑制剂；吡苄明，组胺H1受体拮抗剂；FPL55712，过敏反应慢反应物质白三烯成分的拮抗剂；酚妥拉明，一种α肾上腺素能阻滞剂。这种药理学分析表明，类前列腺素物质介导了大部分过敏毒素的血管收缩作用，白三烯在C3a的情况下有生物学意义的参与，组胺在C5a的情况下有生物学意义的参与。根据先前对活化补体的暴露情况，研究了个体组织对过敏毒素反应的高度变异性。在处死前2小时，给五只豚鼠静脉注射眼镜蛇毒因子（200微克）。与盐水处理的动物相比，这种处理使血清C3和C5浓度分别降至9%和32%。从眼镜蛇毒因子处理的动物中切除的门静脉对C3a的敏感性降低，但对C5a的反应正常。体内补体激活后对C3a的选择性脱敏可能与C3a对血管的高度快速耐受性作用有关。
