Anandamide inhibits transport-related oxygen consumption in the loop of Henle by activating CB1 receptors.
Anandamide inhibits transport-related oxygen consumption in the loop of Henle by activating CB1 receptors.
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Anandamide 通过激活 CB1 受体来抑制亨利环中与运输相关的耗氧量。
DOI：
10.1152/ajprenal.00239.2012
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
García,NéstorH
中科院分区：
文献类型：
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作者：
Silva,GuillermoB;Atchison,DouglasK;Juncos,LuisI;García,NéstorH
The energy required for active Na chloride reabsorption in the thick ascending limb (TAL) depends on oxygen consumption and oxidative phosphorylation (OXP). In other cells, Na transport is inhibited by the endogenous cannabinoid anandamide through the activation of the cannabinoid receptors (CB) type 1 and 2. However, it is unclear whether anandamide alters TAL transport and the mechanisms that could be involved. We hypothesized that anandamide inhibits TAL transport via activation of CB1 receptors and NO. For this, we measured oxygen consumption (QO2) in TAL suspensions to monitor the anandamide effects on transport and OXP. Anandamide reduced QO2in a concentration-dependent manner. During Na-K-2Cl cotransport and Na/H exchange inhibition, anandamide did not inhibit TAL QO2. To test the role of the cannabinoid receptors, we used specific agonists and antagonists of CB1 and CB2 receptors. The CB1-selective agonist WIN55212–2 reduced QO2in a concentration-dependent manner. Also, the CB1 receptor antagonist rimonabant blocked the effect of anandamide on QO2. In contrast, the CB2-selective agonist JHW-133 had no effect on QO2, while the CB2 receptor antagonist AM-630 failed to block the anandamide effects on QO2. To confirm these results, we measured CB1 and CB2 receptor expression and only CB1 expression was detected. Because CB1 receptors are strong nitric oxide synthase (NOS) stimulators and NO inhibits transport in TALs, we evaluated the role of NO. Anandamide stimulated NO production and the NOS inhibitorNG-nitro-l-arginine methyl ester blocked the anandamide effects on QO2. We conclude that anandamide inhibits TAL Na transport-related QO2via activation of CB1 receptor and NOS.
