Dose-dependent effects of CRF-like diuretic peptide on transcellular and paracellular transport pathways

Abstract

The mechanism of action of synthetic Culexcorticotropin-releasing factor (CRF)-like diuretic peptide (CCRF-DP) was investigated in isolated, perfused Malpighian tubules of the yellow fever mosquito, Aedes aegypti. Low concentrations of CCRF-DP (10−10 and 10−9 M) caused depolarizing oscillations of the lumen-positive transepithelial voltage ( V t) in Malpighian tubules, whereas high concentrations (10−8 and 10−7 M) first depolarized and then transiently hyperpolarized V t; CCRF-DP always lowered transepithelial resistance ( R t), regardless of voltage depolarization or hyperpolarization. The short-circuit current ( I sc), an electrical estimate of active transepithelial transport of Na and K, remained unchanged at low concentrations of CCRF-DP, but I sc more than doubled at high concentrations. These effects of CCRF-DP suggest dose-dependent sites of action: low concentrations of CCRF-DP affect the paracellular pathway, and high concentrations affect both paracellular and transcellular pathways.