Angiotensin II stimulates water and NaCl intake through separate cell signalling pathways in rats
Angiotensin II stimulates water and NaCl intake through separate cell signalling pathways in rats
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DOI：
10.1113/expphysiol.2008.044446
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Fluharty, Steven J.
中科院分区：
文献类型：
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作者：
Daniels, Derek;Mietlicki, Elizabeth G.;Fluharty, Steven J.
水和NaCl摄入刺激血管紧张素II （AngII）是激素行为效应的经典模型。体外研究表明，AngII 1型（AT(1)）受体刺激细胞内通路，包括蛋白激酶C （PKC）和丝裂原活化蛋白（MAP）激酶活化。先前的研究支持PKC参与血管诱导的水分摄入而不参与NaCl摄入的假设，MAP激酶在注射AngII后参与NaCl消耗而不参与水摄入的假设。目前的实验在大鼠中测试了这些假设，在PKC抑制剂或MAP激酶抑制剂存在或不存在的情况下，使用中心注射AngII。用PKC抑制剂chelerythrine预处理可减少血管损伤诱导的饮水量，但NaCl的摄入不受影响。相比之下，用MAP激酶抑制剂U0126预处理对血管血管损伤诱导的水摄入量没有影响，但会减弱NaCl摄入量。这些数据支持了工作假设，并显著扩展了我们之前的发现和其他人的发现。也许更重要的是，这些实验证明了肽受体系统的显著多样性，并为细胞内信号通路可能具有不同行为相关性的惊人发现提供了支持。
Angiotensin II (AngII) stimulation of water and NaCl intake is a classic model of the behavioural effects of hormones. In vitro studies indicate that the AngII type 1 (AT(1)) receptor stimulates intracellular pathways that include protein kinase C (PKC) and mitogen-activated protein (MAP) kinase activation. Previous studies support the hypotheses that PKC is involved in AngII-induced water, but not NaCl intake and that MAP kinase plays a role in NaCl consumption, but not water intake, after injection of AngII. The present experiments test these hypotheses in rats using central injections of AngII in the presence or absence of a PKC inhibitor or a MAP kinase inhibitor. Pretreatment with the PKC inhibitor chelerythrine attenuated AngII-induced water intake, but NaCl intake was unaffected. In contrast, pretreatment with U0126, a MAP kinase inhibitor, had no effect on AngII-induced water intake, but attenuated NaCl intake. These data support the working hypotheses and significantly extend our earlier findings and those of others. Perhaps more importantly, these experiments demonstrate the remarkable diversity of peptide receptor systems and add support for the surprising finding that intracellular signalling pathways can have divergent behavioural relevance.