Regulation of cortical collecting duct function: effect of endothelin.

We recently showed that endothelin-1 (ET-1) increases cell Ca2+ in the mouse cortical collecting duct. To clarify the cellular action and target cell of ET-1, electrophysiologic techniques and cell Ca2+ measurement were applied to rabbit cortical collecting ducts perfused in vitro. When 10(-8) mol/L ET-1 was added to the bath, a transient increase followed by a sustained increase in cell Ca2+ was observed. A sustained increase in cell Ca2+ lasted 10 to 20 minutes and was associated with a decrease in lumen-negative transepithelial voltage. To confirm the target cell type of ET-1, confocal laser microscopy was used. An increase in cell Ca2+ was observed in the same cell, which also showed an increase in cell Ca2+ in response to arginine vasopressin (AVP), which indicated that the principal cell has ET-1 receptors in the basolateral membrane. When ET-1 was applied to the bath, total cellular membrane resistance (Ri) decreased initially and then gradually increased because of inhibition of the luminal Na+ channel. An initial decrease in Ri was considered an influx of Ca2+ from the basolateral membrane. To further determine the source of an increase in cell Ca2+, the effect of ET-1 was tested in the absence of external Ca2+ and in the presence of a Ca2+ channel blocker in the bath. Cell Ca2+ did not respond to ET-1 in the absence of external Ca2+, a condition in which an AVP-stimulated increase in cell Ca2+ was preserved.(ABSTRACT TRUNCATED AT 250 WORDS)