Endothelin increases [Ca2+]i in M-1 mouse cortical collecting duct cells by a dual mechanism.
We tested the effects of endothelin-1 (ET-1) on intracellular calcium concentration ([Ca2+]i) of cultured M-1 mouse cortical collecting duct cells. [Ca2+]i was measured using fura 2 and a fluorescent imaging system. At a concentration of extracellular calcium ([Ca2+]o) of 1 mM, ET-1 (10(-12) to 10(-7) M) increased [Ca2+]i. A second application of ET-1 had no effect on Ca2+. In contrast, application of arginine vasopressin after an initial exposure to ET-1 induced a second Ca2+ response. In the absence of extracellular Ca2+ (1 mM EGTA) ET-1 also elicited a Ca2+ peak, indicating participation of Ca2+ release from intracellular stores in the initial Ca2+ peak. At [Ca2+]o of 10 mM, ET-1 also induced an intracellular Ca2+ peak but [Ca2+]i remained significantly elevated. The Ca2+ plateau phase was abolished by nickel (10 or 100 microM) and nifedipine (0.1 or 1 microM). We conclude that ET-1 mediates an increase in [Ca2+]i by Ca2+ release from intracellular stores and activation of a nickel- and nifedipine-sensitive Ca2+ entry mechanism.
Korbmacher
C
C
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Boulpaep
E L
EL
Giebisch
G
G
Geibel
J
J
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D007672:Kidney Cortex; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration
D002121:Calcium Channel Blockers; D016232:Endothelins; D001127:Arginine Vasopressin; D009532:Nickel; D009543:Nifedipine; D002118:Calcium