缓激肽B1和B2受体在小鼠离体气管舒张中的作用

Involvement of bradykinin B1 and B2 receptors in relaxation of mouse isolated trachea.

作者信息

Li L, Vaali K, Paakkari I, Vapaatalo H

机构信息

Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland.

出版信息

Br J Pharmacol. 1998 Apr;123(7):1337-42. doi: 10.1038/sj.bjp.0701741.

DOI:10.1038/sj.bjp.0701741

PMID:9579728

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565297/

Abstract

The aim of the present study was to investigate the effects of bradykinin and [des-Arg9]-bradykinin and their relaxant mechanisms in the mouse isolated trachea. 2. In the resting tracheal preparations with intact epithelium, bradykinin and [des-Arg9]-bradykinin (each drug, 0.01-10 microM) induced neither contraction nor relaxation. In contrast, bradykinin (0.01-10 microM) induced concentration-dependent relaxation when the tracheal preparations were precontracted with methacholine (1 microM). The relaxation induced by bradykinin was inhibited by the B2 receptor antagonist, D-Arg0-[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140, 0.01-1 microM) in a concentration-dependent manner whereas the B1 receptor antagonist, [des-Arg9,Leu8]-bradykinin (0.01-1 microM), had no inhibitory effect on bradykinin-induced relaxation. [des-Arg9]-bradykinin (0.01-10 microM) also caused concentration-dependent relaxation after precontraction with methacholine. The relaxation induced by [des-Arg9-bradykinin was concentration-dependently inhibited by the B1 receptor antagonist, [des-Arg9,Leu8]-bradykinin (0.01-1 microM), whereas the B2 receptor antagonist, Hoe 140 (0.01-1 microM) was without effect. 3. In the presence of the cyclo-oxygenase inhibitor, indomethacin (0.01-1 microM), the relaxations induced by bradykinin and [des-Arg9]-bradykinin were inhibited concentration-dependently. 4. Two nitric oxide (NO) biosynthesis inhibitors NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) and NG-nitro-L-arginine (L-NOARG, 100 microM) had no inhibitory effects on the relaxations induced by bradykinin and [des-Arg9]-bradykinin. Neither did the selective inhibitor of the soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) inhibit the relaxations induced by bradykinin and [des-Arg9]-bradykinin. 5. Prostaglandin E2 (PGE2, 0.01-33 microM) caused concentration-dependent relaxation of the tracheal preparations precontracted with methacholine. Indomethacin (1 microM) and ODQ (10 microM) exerted no inhibitory effects on the relaxation induced by PGE2. 6. The NO-donor, sodium nitroprusside (SNP; 0.01-100 microM) also caused concentration-dependent relaxation of the tracheal preparations precontracted with methacholine. ODQ (0.1-1 microM) concentration-dependently inhibited the relaxation induced by SNP. 7. These data demonstrate that bradykinin and [des-Arg9]-bradykinin relax the mouse trachea precontracted with methacholine by the activation of bradykinin B2-receptors and B1-receptors, respectively. The stimulation of bradykinin receptors induces activation of the cyclo-oxygenase pathway, leading to the production of relaxing prostaglandins. The NO pathway is not involved in the bradykinin-induced relaxation. The relaxation caused by NO-donors in the mouse trachea is likely to be mediated via activation of soluble guanylate cyclase.

摘要

本研究的目的是探讨缓激肽和[去-精氨酸9]-缓激肽在小鼠离体气管中的作用及其舒张机制。2. 在具有完整上皮的静息气管标本中，缓激肽和[去-精氨酸9]-缓激肽（每种药物，0.01 - 10微摩尔）既不引起收缩也不引起舒张。相反，当气管标本用乙酰甲胆碱（1微摩尔）预收缩时，缓激肽（0.01 - 10微摩尔）引起浓度依赖性舒张。缓激肽诱导的舒张被B2受体拮抗剂D-精氨酸0-[Hyp3,Thi5,D-Tic7,Oic8]-缓激肽（Hoe 140，0.01 - 1微摩尔）以浓度依赖性方式抑制，而B1受体拮抗剂[去-精氨酸9,亮氨酸8]-缓激肽（0.01 - 1微摩尔）对缓激肽诱导的舒张没有抑制作用。[去-精氨酸9]-缓激肽（0.01 - 10微摩尔）在与乙酰甲胆碱预收缩后也引起浓度依赖性舒张。[去-精氨酸9]-缓激肽诱导的舒张被B1受体拮抗剂[去-精氨酸9,亮氨酸8]-缓激肽（0.01 - 1微摩尔）浓度依赖性抑制，而B2受体拮抗剂Hoe 140（0.01 - 1微摩尔）没有作用。3. 在环氧化酶抑制剂吲哚美辛（0.01 - 1微摩尔）存在下，缓激肽和[去-精氨酸9]-缓激肽诱导的舒张被浓度依赖性抑制。4. 两种一氧化氮（NO）生物合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME，100微摩尔）和NG-硝基-L-精氨酸（L-NOARG，100微摩尔）对缓激肽和[去-精氨酸9]-缓激肽诱导的舒张没有抑制作用。可溶性鸟苷酸环化酶的选择性抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ，10微摩尔）也不抑制缓激肽和[去-精氨酸9]-缓激肽诱导的舒张。5. 前列腺素E2（PGE2，0.01 - 33微摩尔）使与乙酰甲胆碱预收缩的气管标本产生浓度依赖性舒张。吲哚美辛（1微摩尔）和ODQ（10微摩尔）对PGE2诱导的舒张没有抑制作用。6. NO供体硝普钠（SNP；0.01 - 100微摩尔）也使与乙酰甲胆碱预收缩的气管标本产生浓度依赖性舒张。ODQ（0.1 - 1微摩尔）浓度依赖性抑制SNP诱导的舒张。7. 这些数据表明，缓激肽和[去-精氨酸9]-缓激肽分别通过激活缓激肽B2受体和B1受体使与乙酰甲胆碱预收缩的小鼠气管舒张。缓激肽受体的刺激诱导环氧化酶途径的激活，导致产生舒张性前列腺素。NO途径不参与缓激肽诱导的舒张。NO供体在小鼠气管中引起的舒张可能是通过可溶性鸟苷酸环化酶的激活介导的。