Bradykinin increases Na(+)-K(+) pump activity in cultured guinea-pig tracheal smooth muscle cells.

Bradykinin increases Na(+)-K(+) pump activity in cultured guinea-pig tracheal smooth muscle cells.
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缓激肽可增加培养的豚鼠气管平滑肌细胞中的 Na( )-K( ) 泵活性。

DOI:
10.1038/sj.bjp.0704198
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发表时间:
2001
影响因子:
7.3
通讯作者:
Rhoden,KJ
Rhoden,KJ
中科院分区:
医学2区
文献类型:
--
作者:
Dodson,AM;Rhoden,KJ

文献摘要

被引文献

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通过测定培养豚鼠气管平滑肌细胞对瓦阿因敏感型86rb +的摄取,探讨缓激肽对气道平滑肌Na+‐K+泵的影响。缓激肽诱导乌巴因敏感型86rb +摄取浓度依赖性增加,ec50为3 nM(pD2=8.50±0.10)。吲哚美辛(1 μM)对刺激没有影响,表明它不是由花生四烯酸的环加氧酶产物介导的。b1受体激动剂Lys - des - Arg9 - bradykinin和des - Arg9 - bradykinin对乌巴因敏感的86rb +摄取没有影响。相比之下,b1和b2受体激动剂Lys - bradykinin诱导乌阿巴因敏感的86rb +摄取浓度依赖性增加,ec50为6 nM(pD2=8.21±0.20)。b1受体拮抗剂des - Arg10 - HOE 140 (1 μM)对缓激肽刺激的瓦巴因敏感的86rb +摄取没有影响。b2受体拮抗剂HOE 140和WIN 64338可拮抗缓激肽刺激的瓦巴因敏感型86rb +摄取,pkb值(- log M)分别为8.20±0.08和8.11±0.20。将细胞外Na+从146mmt减少到11mmt,可导致基础瓦巴因敏感型86rb +摄取减少53.5%,并消除缓激肽诱导的摄取。Na+ - H+交换剂的两种抑制剂,甲基异丁基-阿米洛利(MIA, 1-100 μM)和乙基异丙基-阿米洛利(EIPA, 0.1-10 μM),抑制缓激肽刺激的华阿巴因敏感型86rb +摄取,而不影响基础摄取。这些结果表明,缓激肽增加了豚鼠气管平滑肌的Na+‐K+泵活性,刺激了b2受体和Na+‐H+交换器的激活。英国药理学杂志(2001)133,1339-1345;doi: 10.1038 / sj.bjp.0704198
The effect of bradykinin on the Na+‐K+pump of airway smooth muscle was investigated by measuring ouabain‐sensitive86Rb+uptake in cultured guinea‐pig tracheal smooth muscle cells.Bradykinin induced a concentration‐dependent increase in ouabain‐sensitive86Rb+uptake, with an EC50of 3 nM(pD2=8.50±0.10). Stimulation was not affected by indomethacin (1 μM) suggesting that it is not mediated by cycloxygenase products of arachidonic acid.The B1receptor agonists Lys‐des‐Arg9‐bradykinin and des‐Arg9‐bradykinin had no effect on ouabain‐sensitive86Rb+uptake. In contrast, the B1and B2receptor agonist Lys‐bradykinin induced a concentration‐dependent increase in ouabain‐sensitive86Rb+uptake with an EC50of 6 nM(pD2=8.21±0.20).The B1receptor antagonist des‐Arg10‐HOE 140 (1 μM) had no effect on bradykinin‐stimulated ouabain‐sensitive86Rb+uptake. The B2receptor antagonists HOE 140 and WIN 64338 antagonized bradykinin‐stimulated ouabain‐sensitive86Rb+uptake with pKBvalues (−log M) of 8.20±0.08 and 8.11±0.20 respectively.Reducing extracellular Na+from 146 mMto 11 mMcaused a 53.5% decrease in basal ouabain‐sensitive86Rb+uptake and abolished bradykinin‐induced uptake. Two inhibitors of the Na+‐H+exchanger, methylisobutyl‐amiloride (MIA; 1–100 μM) and ethylisopropyl‐amiloride (EIPA; 0.1–10 μM), inhibited bradykinin‐stimulated ouabain‐sensitive86Rb+uptake without affecting basal uptake.These results suggest that bradykinin increases Na+‐K+pump activity of guinea‐pig tracheal smooth muscleviastimulation of B2receptors and activation of the Na+‐H+exchanger.British Journal of Pharmacology(2001)133, 1339–1345; doi:10.1038/sj.bjp.0704198