title: Excretion of NaCl and KCl loads in mosquitoes. 2. Effects of the small molecule Kir channel modulator VU573 and its inactive analog VU342.
abstract: 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 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 of AeKir1, an Aedes inward 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 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 μM VU573 affects Kir channels systemically, including those that might be involved in the release of diuretic hormones.
authors: Department of Entomology, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, Ohio;
authors: Matthew F
authors: MF
authors: Rouhier
authors: Department of Biomedical Sciences, Cornell University, Ithaca, New York; and.
authors: Rebecca M
authors: RM
authors: Hine
authors: Department of Biomedical Sciences, Cornell University, Ithaca, New York; and.
authors: Seokhwan Terry
authors: ST
authors: Park
authors: Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors: Rene
authors: R
authors: Raphemot
authors: Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors: Jerod
authors: J
authors: Denton
authors: Department of Entomology, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, Ohio;
authors: Peter M
authors: PM
authors: Piermarini
authors: Department of Biomedical Sciences, Cornell University, Ithaca, New York; and kwb1@cornell.edu.
authors: Klaus W
authors: KW
authors: Beyenbach
mesh_terms: D000330:Aedes; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide; D006458:Hemolymph / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D007097:Imines / Q000494:pharmacology*; D007552:Isotonic Solutions; D008317:Malpighian Tubules / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011189:Potassium Chloride / Q000378:metabolism*; D000077331:Ringer's Solution; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism*
chemical_list: C585410:1-(3-benzyl-2-imino-2,3-dihydro-1H-benzo(d)imidazol-1-yl)-3-(p-tolyloxy)propan-2-ol; D001562:Benzimidazoles; D006728:Hormones; D007097:Imines; D007552:Isotonic Solutions; D002034:Bumetanide; D012965:Sodium Chloride; D011189:Potassium Chloride; D000077331:Ringer's Solution; D012964:Sodium; D011188:Potassium
keywords: Malpighian tubules; VU573 block of Kir channel; excretion in mosquitoes; inhibition of electrolyte and fluid secretion; renal failure