Endothelin 1 increases cell calcium in mouse collecting tubule cells.
Effects of endothelin 1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) were examined in superfused single-nephron segments dissected from mouse kidney. ET-1, 10(-9) to 10(-6) M, caused a biphasic increase in [Ca2+]i consisting of an initial rapid rise followed by a second more sustained elevation in [Ca2+]i in cortical collecting tubules (CCT), outer medullary CT (OMCT), and inner medullary CT (IMCT). The magnitude of the response was dose dependent and was greater in CCT than in OMCT or IMCT. Additional studies using CCT revealed that Ca2+ removal from the superfusate resulted in attenuation of the second phase of [Ca2+]i with approximately 50% reduction in the height of the initial [Ca2+]i peak in response to 10(-6) M ET-1. Ca2+ channel blocker nicardipine had little effect on ET-1-evoked changes in [Ca2+]i. BAY K 8644 and high superfusate K+ also did not affect [Ca2+]i. Addition of ET-1 and arginine vasopressin (AVP), 10(-6) M each, showed the presence of homologous desensitization but the absence of heterologous desensitization in [Ca2+]i changes. There was no additive effect of ET-1 and AVP on [Ca2+]i when they were added together. These data show that ET-1 evokes a biphasic increase in [Ca2+]i of collecting tubules and suggest that the initial peak of the ET-1-evoked rise in [Ca2+]i is largely due to cell Ca2+ release and that the second sustained rise in [Ca2+]i is largely due to increased Ca2+ influx. Data also suggest that ET-1 and AVP may act in the collecting tubules through different receptors.
Naruse
M
M
First Department of Internal Medicine, University of Tokyo Faculty of Medicine, Japan.
Uchida
S
S
Ogata
E
E
Kurokawa
K
K
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D009529:Nicardipine / Q000494:pharmacology; D009994:Osmolar Concentration
D016232:Endothelins; D001127:Arginine Vasopressin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009529:Nicardipine; D002118:Calcium