Excretion of NaCl and KCl loads in mosquitoes. 2. Effects of the small molecule Kir channel modulator VU573 and its inactive analog VU342.
Excretion of NaCl and KCl loads in mosquitoes. 2. Effects of the small molecule Kir channel modulator VU573 and its inactive analog VU342.
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蚊子体内 NaCl 和 KCl 负荷的排泄。
DOI：
10.1152/ajpregu.00106.2014
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Beyenbach,KlausW
中科院分区：
文献类型：
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作者：
Rouhier,MatthewF;Hine,RebeccaM;Park,SeokhwanTerry;Raphemot,Rene;Denton,Jerod;Piermarini,PeterM;Beyenbach,KlausW
本文研究了两种小分子药物VU 342和VU 573对埃及伊蚊肾功能的影响。在分离的马氏管中，VU 342（10 μM）对Na+、K+、Cl−和水的跨上皮分泌无影响。相比之下，当肾小管沐浴在富含Na+或K+的林格氏溶液中时，10 μM VU 573首先刺激然后抑制液体的经上皮分泌。早期刺激被布美他尼阻断，提示短暂刺激Na-K-2Cl共转运，晚期抑制液体分泌与已知VU 573阻断AeKir 1（Aedes内向整流性K+通道）一致。血淋巴浓度约为11 μM的VU 342和VU 573对血淋巴Na+或K+负荷引发的利尿作用没有影响。血淋巴浓度为420 μM的VU 342对血淋巴Na+或K+负荷引起的利尿作用无影响。相反，相同浓度的VU 573通过抑制Na+、Cl−和水的尿排泄而显著减少Na+利尿。在K+负载的蚊子中，420 μM VU 573通过抑制尿液中K+、Na+、Cl−和水的排泄，显著减少K+利尿作用。我们的结论是：1）在离体马氏管中观察到的VU 573的作用在体内被Na+和K+负荷共同注射触发的利尿作用所压倒; 2）在420 μM血淋巴浓度下，VU 573全身性地影响Kir通道，包括那些可能参与利尿激素释放的通道。
The effect of two small molecules VU342 and VU573 on renal functions in the yellow fever mosquitoAedes aegyptiwas investigated in vitro and in vivo. In isolated Malpighian tubules, VU342 (10 μM) had no effect on the transepithelial secretion of Na+, K+, Cl−, and water. In contrast, 10 μM VU573 first stimulated and then inhibited the transepithelial secretion of fluid when the tubules were bathed in Na+-rich or K+-rich Ringer solution. The early stimulation was blocked by bumetanide, suggesting the transient stimulation of Na-K-2Cl cotransport, and the late inhibition of fluid secretion was consistent with the known block ofAeKir1, anAedesinward rectifier K+channel, by VU573. VU342 and VU573 at a hemolymph concentration of about 11 μM had no effect on the diuresis triggered by hemolymph Na+or K+loads. VU342 at a hemolymph concentration of 420 μM had no effect on the diuresis elicited by hemolymph Na+or K+loads. In contrast, the same concentration of VU573 significantly diminished the Na+diuresis by inhibiting the urinary excretion of Na+, Cl−, and water. In K+-loaded mosquitoes, 420 μM VU573 significantly diminished the K+diuresis by inhibiting the urinary excretion of K+, Na+, Cl−, and water. We conclude that1) the effects of VU573 observed in isolated Malpighian tubules are overwhelmed in vivo by the diuresis triggered with the coinjection of Na+and K+loads, and2) at a hemolymph concentration of 420 μM VU573 affects Kir channels systemically, including those that might be involved in the release of diuretic hormones.