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Now using the kinins of Aedes (the aedeskinins), we have found that in isolated Aedes Malpighian tubules all three aedeskinins (1 \u03bcM) significantly 1) increased the rate of fluid secretion (V\u0307<jats:sub>S<\/jats:sub>), 2) hyperpolarized the basolateral membrane voltage (V<jats:sub>bl<\/jats:sub>), and 3) decreased the input resistance (R<jats:sub>in<\/jats:sub>) of principal cells, consistent with the known increase in the Cl<jats:sup>\u2212<\/jats:sup>conductance of the paracellular pathway in Aedes Malpighian tubules. Aedeskinin-III, studied in further detail, significantly increased V\u0307<jats:sub>S<\/jats:sub>with an EC<jats:sub>50<\/jats:sub>of 1.5 \u00d7 10<jats:sup>\u22128<\/jats:sup>M. In parallel, the Na<jats:sup>+<\/jats:sup>concentration in secreted fluid significantly decreased, and the K<jats:sup>+<\/jats:sup>concentration significantly increased. The concentration of Cl<jats:sup>\u2212<\/jats:sup>remained unchanged. While the three aedeskinins triggered effects on V<jats:sub>bl<\/jats:sub>, R<jats:sub>in<\/jats:sub>, and V\u0307<jats:sub>S<\/jats:sub>, synthetic kinin analogs, which contain modifications of the COOH-terminal amide pentapeptide core sequence critical for biological activity, displayed variable effects. For example, kinin analog 1578 significantly stimulated V\u0307<jats:sub>S<\/jats:sub>but had no effect on V<jats:sub>bl<\/jats:sub>and R<jats:sub>in<\/jats:sub>, whereas kinin analog 1708 had no effect on V\u0307<jats:sub>S<\/jats:sub>but significantly affected V<jats:sub>bl<\/jats:sub>and R<jats:sub>in<\/jats:sub>. These observations suggest separate signaling pathways activated by kinins. One triggers the electrophysiological response, and the other triggers fluid secretion. It remains to be determined whether the two signaling pathways emanate from a single kinin receptor via agonist-directed signaling or from a differentially glycosylated receptor. Occasionally, Malpighian tubules did not exhibit a detectable response to natural and synthetic kinins. 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