The stable VIP analogue, Ro 24-9981, potentiates bradykinin-induced increases in clearance of macromolecules.
The stable VIP analogue, Ro 24-9981, potentiates bradykinin-induced increases in clearance of macromolecules.
复制标题
稳定的 VIP 类似物 Ro 24-9981 可增强缓激肽诱导的大分子清除率增加。
DOI：
10.1152/ajpheart.1995.269.5.h1648
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Rubinstein,I
中科院分区：
文献类型：
--
作者：
Gao,XP;Rubinstein,I
本研究的目的是确定人血管活性肠肽的稳定环肽类似物Ro 24-9981是否调节缓激肽诱导的口腔粘膜血浆渗出，如果是，确定介导这些反应的机制。使用活体显微镜，我们发现Ro 24-9981的充分暴露对仓鼠颊囊中荧光素-异硫氰酸酯-葡聚糖（摩尔质量70 kDa）的渗漏部位形成和清除无显著影响。然而，Ro 24-9981显著增强缓激肽诱导的渗漏部位形成和荧光素-异硫氰酸酯-葡聚糖清除的增加（P < 0.05）。这些效应具有特异性，因为Ro 24-9981对腺苷和钙离子载体A23187诱导的渗漏部位形成和荧光素-异硫氰酸酯-葡聚糖清除率增加无显著影响。此外，它们不是由花生四烯酸代谢的环氧合酶产物介导的，因为吲哚美辛无效。NO合成酶抑制剂NG-硝基-L-精氨酸甲酯（NG-nitro-D-arginine methyl ester）可显著减弱缓激肽和Ro 24-9981对缓激肽的作用（P < 0.05）。这些反应被L-精氨酸而不是D-精氨酸恢复。总的来说，这些数据表明，缓激肽诱导的血浆渗出在口腔粘膜中被Ro 24-9981以特异性受体介导的方式增强。这些反应是介导的，部分，由L-精氨酸/一氧化氮生物合成途径。
The purpose of this study was to determine whether the stable cyclic peptide analogue of human vasoactive intestinal peptide, Ro 24-9981, modulates bradykinin-induced plasma exudation in the oral mucosa and if so, to determine the mechanisms that mediated these responses. Using intravital microscopy, we found that suffusion of Ro 24-9981 had no significant effects on leaky site formation and clearance of fluorescein-isothiocyanate-dextran (mol mass 70 kDa) in the hamster cheek pouch. However, Ro 24-9981 significantly potentiated bradykinin-induced increases in leaky site formation and clearance of fluorescein-isothiocyanate-dextran (P < 0.05). These effects were specific because Ro 24-9981 had no significant effects on adenosine and calcium ionophore A23187-induced increases in leaky site formation and clearance of fluorescein-isothiocyanate-dextran. Furthermore, they were not mediated by cyclooxygenase products of arachidonic acid metabolism because indomethacin was ineffective. NG-nitro-L-arginine methyl ester, a selective inhibitor of nitric oxide synthase, but not NG-nitro-D-arginine methyl ester, significantly attenuated the effects of both bradykinin and Ro 24-9981 with bradykinin (P < 0.05). These responses were restored by L-arginine but not D-arginine. Collectively, these data indicate that bradykinin-induced plasma exudation in the oral mucosa was potentiated by Ro 24-9981 in a specific receptor-mediated fashion. These responses were mediated, in part, by the L-arginine/nitric oxide biosynthetic pathway.