Griesbacher T, Lembeck F
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Br J Pharmacol. 1987 Oct;92(2):333-40. doi: 10.1111/j.1476-5381.1987.tb11328.x.
1 The inhibition of the bradykinin-induced plasma extravasation by six bradykinin (Bk) antagonists was tested on rabbit skin. All of them showed inhibitory effects without an agonistic action in the does used. B4310 (Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk) was the most active antagonist and was therefore used in the subsequent experiments. 2 B4310 (5-500 nM) antagonized the bradykinin-induced reduction of the venous outflow from the rabbit isolated ear in dose-dependent manner without affecting the arterial vasoconstriction induced by angiotensin II. 3 The bradykinin-induced release of prostaglandin E2 (PGE2) from the perfused rabbit ear was reduced by 63% when B4310 (800 nM) was infused before, during and after the bradykinin injection. 4 Bradykinin was injected into the ear artery of anaesthetized rabbits and the reflex hypotensive response was used as indicator of the nociception. The response was antagonized by a local infusion of B4310 (50 and 500 nM). The antagonism was dose-dependent and reversible. The parallel shift of the dose-response curve to bradykinin suggests a competitive inhibition. However, B4310 did not antagonize acetylcholine-induced nociceptor stimulation. 5 B4310 inhibited bradykinin-induced stimulation of the trigeminal nerve which results in a substance P-mediated contraction of the iris sphincter muscle. A pA2 of 7.59 was calculated. B4310 did not inhibit capsaicin-induced contractions. 6 It is concluded that B4310 inhibits specifically five different actions of bradykinin which are related to its possible pathophysiological role.
1 在兔皮肤上测试了六种缓激肽（Bk）拮抗剂对缓激肽诱导的血浆外渗的抑制作用。在所使用的剂量下，它们均显示出抑制作用，且无激动作用。B4310（Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk）是活性最强的拮抗剂，因此用于后续实验。2 B4310（5 - 500 nM）以剂量依赖性方式拮抗缓激肽诱导的兔离体耳静脉流出量减少，而不影响血管紧张素II诱导的动脉血管收缩。3 在缓激肽注射前、注射期间和注射后输注B4310（800 nM）时，缓激肽诱导的灌注兔耳中前列腺素E2（PGE2）释放减少了63%。4 向麻醉兔的耳动脉注射缓激肽，并将反射性降压反应用作伤害感受的指标。局部输注B4310（50和500 nM）可拮抗该反应。这种拮抗作用具有剂量依赖性且可逆。剂量 - 反应曲线向缓激肽的平行移动表明是竞争性抑制。然而，B4310不拮抗乙酰胆碱诱导的伤害感受器刺激。5 B4310抑制缓激肽诱导的三叉神经刺激，这会导致P物质介导的虹膜括约肌收缩。计算出的pA2为7.59。B4310不抑制辣椒素诱导的收缩。6 得出结论，B4310特异性抑制缓激肽的五种不同作用，这些作用与其可能的病理生理作用相关。
