Griesbacher T
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Naunyn Schmiedebergs Arch Pharmacol. 1992 Jul;346(1):102-7. doi: 10.1007/BF00167578.
Both bradykinin (BK) and des-Arg9-BK induced relaxations of the isolated longitudinal smooth muscles of the rat duodenum. No contractile effects were observed with both peptides at concentrations up to 1 mumol/l. Des-Arg9-BK was about 1000 times less potent than BK. The novel B2 antagonist HOE 140 (D-Arg-[Hyp3, Thi5, D-Phe7, Oic8]-BK) potently inhibited the BK-induced relaxations, but did not affect the relaxations induced by des-Arg9-BK. Conversely, the B1 receptor antagonist des-Arg9-[Leu8]-BK only inhibited des-Arg9-BK, but did not affect BK-induced relaxations. The relaxations induced by BK and by des-Arg9-BK were inhibited by apamin (1 mumol/l) demonstrating that apamin-sensitive K+ channels are involved. In contrast, tetraethylammonium (1 mmol/l) did not inhibit the relaxations. BK-induced relaxations were reduced by about 25% in the presence of indomethacin (10 mumol/l) although the concentration-response curve to BK was not shifted to the left. Prostaglandin E1 caused relaxations with a pD2 value of 9.2. It is concluded that both BK and des-Arg9-BK can elicit relaxations of the rat duodenum via pharmacologically distinct kinin receptor subtypes, but via similar effector mechanisms.
缓激肽（BK）和去-精氨酸9-缓激肽（des-Arg9-BK）均可使大鼠十二指肠离体纵行平滑肌舒张。在浓度高达1μmol/L时，两种肽均未观察到收缩作用。des-Arg9-BK的效力约为BK的1000分之一。新型B2拮抗剂HOE 140（D-精氨酸-[Hyp3, Thi5, D-苯丙氨酸7, Oic8]-BK）能有效抑制BK诱导的舒张，但不影响des-Arg9-BK诱导的舒张。相反，B1受体拮抗剂去-精氨酸9-[亮氨酸8]-BK仅抑制des-Arg9-BK，而不影响BK诱导的舒张。阿帕明（1μmol/L）可抑制BK和des-Arg9-BK诱导的舒张，表明阿帕明敏感的钾通道参与其中。相比之下，四乙铵（1mmol/L）不抑制舒张。在吲哚美辛（10μmol/L）存在的情况下，BK诱导的舒张降低了约25%，尽管BK的浓度-反应曲线未向左移动。前列腺素E1可引起舒张，其pD2值为9.2。结论是，BK和des-Arg9-BK均可通过药理学上不同的激肽受体亚型，但通过相似的效应机制，引起大鼠十二指肠舒张。
