Hanson J M, Morley J, Soria-Herrera C
Br J Pharmacol. 1974 Mar;50(3):383-92. doi: 10.1111/j.1476-5381.1974.tb09613.x.
1 Peptide 401, a potent mast cell degranulating factor from bee venom, substantially inhibited the oedema provoked by subplantar injection of carrageenin or intra-articular injection of turpentine in the rat. The ED(50) of 401 was c. 0.1 mg/kg. The anti-inflammatory effect was assessed by measurement of the increased (125)I-albumin content of an injected site in comparison with an uninjected contralateral site.2 Peptide 401 also suppressed the increased vascular permeability due to intradermal injection of various smooth muscle spasmogens (histamine, bradykinin, 5-hydroxytryptamine (5-HT), and prostaglandins).3 Other comparable mast cell degranulating agents (48/80 and melittin) showed little evidence of anti-inflammatory activity when tested at comparable dosage on turpentine arthritis and carrageenin oedema.4 The anti-inflammatory effects were not abolished by pretreatment with mepyramine and methysergide, which abolished the increased vascular permeability produced by local injection of 401.5 The anti-inflammatory action of 401 was not affected by regional denervation or pretreatment with phenoxybenzamine, and was reduced but not abolished by adrenalectomy.6 Measurement of skin temperature, fractional extraction of (86)Rb and blood flow in perfused mesentery gave no evidence that the anti-inflammatory action of 401 was due to reduced tissue perfusion.7 It is concluded that 401 may exert its anti-inflammatory action directly by making the vascular endothelium anergic to phlogistic stimuli.
肽401是一种来自蜂毒的强效肥大细胞脱颗粒因子,它能显著抑制大鼠足底注射角叉菜胶或关节腔内注射松节油所引发的水肿。401的半数有效剂量(ED50)约为0.1毫克/千克。通过测量注射部位与未注射的对侧部位相比增加的(125)I - 白蛋白含量来评估其抗炎作用。
肽401还能抑制因皮内注射各种平滑肌痉挛剂(组胺、缓激肽、5 - 羟色胺(5 - HT)和前列腺素)而导致的血管通透性增加。
当以可比剂量测试其他类似的肥大细胞脱颗粒剂(48/80和蜂毒肽)对松节油性关节炎和角叉菜胶性水肿的抗炎活性时,几乎没有发现它们有抗炎活性的证据。
用甲氧苄胺嘧啶和甲基麦角新碱预处理并不能消除401的抗炎作用,而这两种药物却能消除局部注射401所产生的血管通透性增加。
401的抗炎作用不受局部去神经支配或用苯氧苄胺预处理的影响,而肾上腺切除可使其抗炎作用减弱但并未消除。
测量皮肤温度、(86)Rb的分数提取以及灌注肠系膜中的血流量,均未发现401的抗炎作用是由于组织灌注减少所致。
得出的结论是,401可能通过使血管内皮细胞对炎症刺激无反应而直接发挥其抗炎作用。