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)
First Department of Internal Medicine, University of Tokyo, Japan.
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Kurokawa
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Yoshitomi
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M
Ikeda
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Uchida
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Naruse
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Imai
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D003592:Cytophotometry; D004095:Dihydropyridines / Q000494:pharmacology; D016232:Endothelins / Q000502:physiology*; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D007834:Lasers; D008853:Microscopy / Q000379:methods; D009578:Nitrobenzenes; D010879:Piperazines; D011817:Rabbits
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D016232:Endothelins; D009578:Nitrobenzenes; D010879:Piperazines; D001127:Arginine Vasopressin; C054218:manidipine; D002118:Calcium