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

The mechanism of action of synthetic Culex corticotropin-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 (Vt) in Malpighian tubules, whereas high concentrations (10(-8) and 10(-7) M) first depolarized and then transiently hyperpolarized Vt; CCRF-DP always lowered transepithelial resistance (Rt), regardless of voltage depolarization or hyperpolarization. The short-circuit current (Isc), an electrical estimate of active transepithelial transport of Na and K, remained unchanged at low concentrations of CCRF-DP, but Isc 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.