Fig. 1. Proposed model of ion transport in mosquito Malpighian tubules. Blood feeding initiates the release of diuretic peptides that trigger activation of ion channels in Malpighian tubules. Acute activation may result from a cAMP-mediated pathway controlling diuresis. The electrochemical gradient established by the vacuolar type-proton ATPase (V-ATPase) energizes secondary transport of intracellular ions and thus of fluid secretion through the apical membrane transporters. The secondary transporter(s) coupled to V-ATPase activity possesses pharmacological properties similar to sodium/proton exchangers (NHEs), whereas basolateral transport activated through cAMP is proposed to involve bumetanide-sensitive cation-coupled chloride cotransporters (CCCs). In the Malpighian tubules, the Na⁺/K⁺-ATPase is expressed on the basolateral membrane of proximal principal cells but not in distal principal cells.