The @entity4224 @entity4224 is an important vector of @entity1800 that impact global health. Insecticides are typically used to manage mosquito populations, but the evolution of insecticide resistance is limiting their effectiveness. Thus, identifying new molecular and physiological targets in mosquitoes is needed to facilitate insecticide discovery and development. Here we test the hypothesis that gap junctions are valid molecular and physiological targets for new insecticides. Gap junctions are intercellular channels that mediate direct communication between neighboring cells and consist of evolutionarily distinct proteins in vertebrate (connexins) and invertebrate (innexins) animals. We show that the injection of pharmacological inhibitors of gap junctions (i.e., @entity8743 , @entity5728 , or @entity8775 ) into the hemolymph of adult female mosquitoes elicits dose-dependent toxic effects, with @entity8775 showing the greatest potency. In contrast, when applied topically to the cuticle, @entity8743 was the only inhibitor to exhibit full efficacy. In vivo urine excretion assays demonstrate that both @entity8743 and @entity8775 inhibit the diuretic output of adult female mosquitoes, suggesting inhibition of excretory functions as part of their mechanism of action. When added to the rearing water of 1st instar larvae, @entity8743 and @entity5728 both elicit dose-dependent toxic effects, with @entity5728 showing the greatest potency. Injecting a double-stranded RNA cocktail against innexins into the hemolymph of adult female mosquitoes knock down whole-animal innexin mRNA expression and decreases survival of the mosquitoes. Taken together these data indicate that gap junctions may provide novel molecular and physiological targets for the development of insecticides.

Pharmacological and Genetic Evidence for Gap Junctions as Potential New Insecticide Targets in the @entity4224 , XXXX .

@entity4224 :: ('7159', 'Species') :: ['yellow fever mosquito', 'Aedes aegypti'] @entity8743 :: ('MESH:D002229', 'Chemical') :: ['carbenoxolone'] @entity5728 :: ('MESH:D008469', 'Chemical') :: ['meclofenamic acid'] @entity1800 :: ('MESH:D014777', 'Disease') :: ['viral diseases'] @entity8775 :: ('MESH:D015767', 'Chemical') :: ['mefloquine']
@entity4224 :: (7159,Species) :: ['Aedes aegypti']
