Female Aedes aegypti mosquitoes face the challenge of excess water and ion intake after a blood meal. To cope with this, female A. aegypti have a highly active excretory system that includes the Malpighian tubules (MTs), which are under rigorous control by several neuroendocrine factors to regulate transepithelial movement of ions and osmotically-obliged water. CAPA neuropeptides, produced in the CNS are evolutionarily related to the vertebrate neuromedinU peptides. While extensive studies have investigated the effects of CAPA peptides on diuresis, the role of CAPA in adult A. aegypti remains unclear. Given that CAPA receptor transcript was localized to the principal cells of the MTs, the objectives of the study were to identify the components of the signaling cascade leading to CAPA-induced inhibition of fluid secretion. Through fluid secretion assays, it was shown that CAPA inhibits fluid secretion by tubules stimulated with specific diuretics, 5HT and DH₃₁, whilst maintaining the relative Na⁺ and K⁺ transport in the MTs. Interestingly, CAPA was found to not influence CRF-stimulated secretion in the tubules. Pharmacological inhibition of PKG/NOS signalling abolishes the anti-diuretic activity of CAPA, confirming its role in the CAPA signaling pathway. Furthermore, MTs treated with bafilomycin, a proton pump inhibitor, was found to inhibit fluid secretion stimulated by 5HT and DH₃₁, while having no inhibitory action on CRF-stimulated MTs. Additionally, alkalization of the secreted fluid in response to CAPA suggests inhibition of the proton pump, which may lead to constrained cation entry across the apical membrane of the MTs. Further understanding the role of each specific hormone family, including both diuretic and anti-diuretic factors, will help resolve this complex regulatory network.