Excretion of NaCl and KCl loads in mosquitoes. 2. Effects of the small molecule Kir channel modulator VU573 and its inactive analog VU342
Autor(es): Rouhier, Matthew F.; Hine, Rebecca M.; Park, Seokhwan Terry; Raphemot, Rene; Denton, Jerod; Piermarini, Peter M.; Beyenbach, Klaus W.
Resumo: The effect of two small molecules VU342 and VU573 on renal functions in the yellow fever mosquito Aedes aegypti was investigated in vitro and in vivo. In isolated Malpighian tubules, VU342 (10 mu M) had no effect on the transepithelial secretion of Na+, K+, Cl-, and water. In contrast, 10 mu M 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 of AeKir1, an Aedes inward rectifier K+ channel, by VU573. VU342 and VU573 at a hemolymph concentration of about 11 mu M had no effect on the diuresis triggered by hemolymph Na+ or K+ loads. VU342 at a hemolymph concentration of 420 mu M 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 mu M VU573 significantly diminished the K+ diuresis by inhibiting the urinary excretion of K+, Na+, Cl-, and water. We conclude that 1) 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, and 2) at a hemolymph concentration of 420 mu M VU573 affects Kir channels systemically, including those that might be involved in the release of diuretic hormones.
Palavras-Chave: Excretion In Mosquitoes; Inhibition Of Electrolyte And Fluid Secretion; Malpighian Tubules; Renal Failure; VU573 Block Of Kir Channel
Imprenta: American Journal of Physiology-Regulatory Integrative and Comparative Physiology, v. 307, n. 7, p. R850-R861, 2014
Identificador do objeto digital: 10.1152/ajpregu.00106.2014
Descritores: Aedes aegypti - Biochemistry ; Aedes aegypti - Public health
Data de publicação: 2014
