Effects of chronic exposure to dietary salicylate on elimination and renal excretion of salicylate byDrosophila melanogasterlarvae

Abstract

SUMMARY The effects of chronic exposure to dietary salicylate on elimination and renal excretion of salicylate by D. melanogaster larvae were evaluated using salicylate-selective microelectrodes. Larvae chronically exposed to dietary salicylate showed 25% less salicylate in the haemolymph compared to the control group after feeding on a salicylate-enriched diet. By 1 h after transfer to a salicylate-free diet the levels of salicylate in the haemolymph of larvae raised on dietary salicylate were 46% lower than in the control group. Salicylate flux increased dramatically across Malpighian tubules but not across midgut or hindgut isolated from larvae chronically exposed to dietary salicylate, relative to the control group. Malpighian tubules isolated from experimental larvae showed a 4.7-fold increase in Kt and a nearly 5-fold increase in Jmax relative to the control. These changes in salicylate transport were accompanied by a 3.2-fold increase in fluid secretion rate. Moreover, the high rates of fluid secretion by the Malpighian tubules isolated from experimental larvae were stimulated 2.1-fold and 2.8-fold when tubules were challenged with 1 mmol l–1 cAMP and 10 μmol l–1 leucokinin I, respectively. Taken together, these results indicate that chronic exposure of D. melanogaster larvae to dietary salicylate alters elimination of such toxins from the haemolymph and increases the basal rate of fluid secretion and excretion of salicylate by the Malpighian tubules.

Interactions between detoxification mechanisms and excretion in Malpighian tubules ofDrosophila melanogaster

“…We have previously studied the roles of the gut and the Malpighian tubules in the elimination of organic cations (Bijelic et al, 2005;Rheault et al, 2006) and organic anions (Ruiz-Sanchez and O'Donnell, 2007;Chahine and O'Donnell, 2009;Chahine and O'Donnell, 2010). The organic anion methotrexate (MTX) is secreted by the Malpighian tubules of larval and adult Drosophila, and chronic exposure of the larvae to dietary MTX increases both the rate of MTX secretion by the tubules and the expression of multiple transporter genes (Chahine and O'Donnell, 2009;Chahine and O'Donnell, 2010).…”

The effects of altered expression of the Keap1/CncC pathway on the secretion of fluid and salicylate by Malpighian tubules of Drosophila melanogaster

“…Previous studies show that Malpighian tubules isolated from third‐instar D. melanogaster larvae display increased rates of fluid secretion in as little as 24 h after exposure to dietary salicylate (Ruiz‐Sanchez & O'Donnell, ; Chahine & O'Donnell, ). The present study demonstrates for the first time that tubules isolated from adult females at 3–5 days post eclosion and reared from eggs on a diet containing salicylate show significantly increased rates of fluid secretion compared with those measured in tubules dissected from flies reared on a salicylate‐free diet (Fig.…”

“…Salicylate flux across the Malpighian tubules declines when tubules are bathed in Na + ‐free saline, supporting the idea that organic anion transport is facilitated by a Na + co‐transporter (Ruiz‐Sanchez & O'Donnell, ). The addition of cAMP to tubules from salicylate‐fed larvae increases fluid secretion further, which suggests that the increase in the fluid secretion rate in response to dietary salicylate is modulated via the insertion of more ion transporters as opposed to an increase in levels of cAMP and second messengers (Ruiz‐Sanchez & O'Donnell, ). A suggested candidate is the V‐type H + ‐ATPase on the apical membrane; an increase in the number of proton pumps would increase the secretion of Na + , K + and Cl − with a subsequent increase in the rate of secretion of osmotically obliged water (Ruiz‐Sanchez & O'Donnell, ).…”

Oatp58Dc contributes to blood-brain barrier function by excluding organic anions from the Drosophila brain

“…It is also of interest to determine whether compensatory mechanisms alter the phenotype of the BBB in response to loss of Oatp58Dc or other transporter function. In addition, dynamic changes in expression, indicative of phenotypic plasticity, have been observed for Oats when flies are reared on diets enriched in organic anions such as salicylate (11,46). Future studies should be directed at phenotypic plasticity of ion transporters in the BBB.…”