豚鼠体内单一缓激肽B2受体的药理学证据。

Pharmacological evidence for a single bradykinin B2 receptor in the guinea-pig.

作者信息

Pruneau D, Luccarini J M, Defrêne E, Paquet J L, Bélichard P

机构信息

Centre de Recherche, Laboratoires Fournier S.C.A., Daix, France.

出版信息

Br J Pharmacol. 1995 Oct;116(3):2106-12. doi: 10.1111/j.1476-5381.1995.tb16418.x.

DOI:10.1111/j.1476-5381.1995.tb16418.x

PMID:8640352

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908926/

Abstract

The present study addresses the possibility of the existence of different kinin B2 receptor subtypes in the guinea-pig by evaluating the affinity of peptide and nonpeptide receptor antagonists. For this purpose, jugular vein rings, ileum segments, lung parenchymal and trachea strips were set up in organ baths for isometric tension measurements. The experiments were conducted in the presence o indomethacin (3 microM), atropine (10 microM) and captopril (10 microM). 2. BK contracted jugular vein (JV), ileum (GPI), parenchyma (LP) and trachea (GPT) with an EC50 of 13.2 +/- 1.4 nM (n=27), 11.2 +/- 2.1 (n=26), 23.6 +/- 6.3 (n=26), and 33.0 +/- 6.5 (n=27), respectively. Thiorphan, a neutral endopeptidase (EC 3.4.34.11) inhibitor and MERGETPA (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid), a carboxypeptidase inhibitor, had no effect on the BK-induced contractions of JV, GPI and LP. In the GPT, thiorpan potentiated the contractile response to BK and was thus added in the corresponding experiments. 3. The peptide B2 receptor antagonist, Hoe 140 and the nonpeptide compound, WIN 64338, behaved as noncompetitive antagonists against contractile responses to cumulative BK in the four tissues although Hoe 140 appeared as a competitive inhibitor in the GPT only. IN order to compare the inhibitory potency of these compounds between tissues, pKB values were determined. Mean values of pKB for Hoe 140 were 8.05 +/- 0.07, 8.43 +/- 0.11, 8.13 +/- 0.18, and 8.52 +/- 0. 25 in the JV, GPI, GPT and LP, respectively. WIN 64338 gave mean pKB values of 6.89 +/- 0.10, 7.57 +/- 0.12, 7.36 +/- 0.12 adn 7.51 +/- 0.28 in the JV, GPI, LP and GPT, respectively. 4. D-Arg [Hyp3, D-Phe7, Leu8]BK and D-Arg[Hyp3, D-Phe7]BK (NPC 567) inhibited in a competitive fashion the concentration-response curves to BK. Values of pA2for each compound were not significantly different in the four tissues and were between 5.81 and 6.31 for D-Arg [Hyp3, D-Phe7, Leu8]BK and between 5.55 and 5.65 for NPC 567.

摘要

本研究通过评估肽类和非肽类受体拮抗剂的亲和力，探讨豚鼠体内是否存在不同的缓激肽B2受体亚型。为此，将颈静脉环、回肠段、肺实质条和气管条置于器官浴槽中进行等长张力测量。实验在吲哚美辛（3 microM）、阿托品（10 microM）和卡托普利（10 microM）存在的情况下进行。2. 缓激肽使颈静脉（JV）、回肠（GPI）、实质（LP）和气管（GPT）收缩，其EC50分别为13.2±1.4 nM（n = 27）、11.2±2.1（n = 26）、23.6±6.3（n = 26）和33.0±6.5（n = 27）。硫氧还蛋白，一种中性内肽酶（EC 3.4.34.11）抑制剂和MERGETPA（DL - 2 - 巯基甲基 - 3 - 胍基乙基硫代丙酸），一种羧肽酶抑制剂，对缓激肽诱导的JV、GPI和LP收缩无影响。在GPT中，硫氧还蛋白增强了对缓激肽的收缩反应，因此在相应实验中加入。3. 肽类B2受体拮抗剂Hoe 140和非肽类化合物WIN 64338在这四种组织中对缓激肽累积收缩反应表现为非竞争性拮抗剂，尽管Hoe 140仅在GPT中表现为竞争性抑制剂。为了比较这些化合物在不同组织间的抑制效力，测定了pKB值。Hoe 140在JV、GPI、GPT和LP中的pKB平均值分别为8.05±0.07、8.43±0.11、8.13±0.18和8.52±0.25。WIN 64338在JV、GPI、LP和GPT中的pKB平均值分别为6.89±0.10、7.57±0.12、7.36±0.12和7.51±0.28。4. D - Arg [Hyp3, D - Phe7, Leu8]BK和D - Arg[Hyp3, D - Phe7]BK（NPC 567）以竞争性方式抑制缓激肽的浓度 - 反应曲线。每种化合物的pA2值在这四种组织中无显著差异，D - Arg [Hyp3, D - Phe7, Leu8]BK的pA2值在5.81至6.31之间，NPC 567的pA2值在5.55至5.65之间。