Fluoride mobilizes intracellular calcium and promotes Ca2+ influx in rat proximal tubules.
In the renal proximal tubule, external Ca2+ ([Ca2+]o) is required for parathyroid hormone to elevate cytosolic Ca2+ ([Ca2+]i). However, other hormones increase [Ca2+]i in the absence of [Ca2+]o. These differences may arise from a diversity of signal transduction pathways acting on external and internal Ca2+ pools. However, Ca2+ influx may be necessary to expedite and maintain the rise of [Ca2+]i for a period after the initial surge. In this study, F- was used to probe the roles of intracellular Ca2+ mobilization, Ca2+ influx, and phosphoinositide (PI) hydrolysis on the surge of [Ca2+]i in rat proximal tubules. In the presence of external Ca2+; 1-20 mM F- evoked incremental rises of [Ca2+]i in tubules loaded with aequorin. Whereas 10 mM F- increased [Ca2+]i in the absence of [Ca2+]o, the time constant for the [Ca2+]i surge was increased. These findings are consistent with a role of Ca2+ influx on the effect of F- on [Ca2+]i. Indeed, 10 mM F- also enhanced the uptake of 45Ca2+, and promoted Ca2+ influx in aequorin- and fura-2-loaded, Ca(2+)-deprived tubules. In tubules, F- also activated PI hydrolysis with a time course that paralleled Ca2+ mobilization. The effect of F- on [Ca2+]i was not altered when the 39-kDa pertussis toxin substrate was inactivated with the toxin. This G protein was most likely Gi, because prostaglandin E2, an activator of Gi in tubules, dissociated the pertussis toxin-sensitive protein. The results support the notion that activation of a signal-transduction complex, the F- substrate, causes Ca2+ influx, mobilizes internal Ca2+, and activates PI hydrolysis in rat proximal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)
Dominguez
J H
JH
Nephrology Section, Veterans Administration Medical Center, Indianapolis, Indiana 46202.
Garcia
J G
JG
Rothrock
J K
JK
English
D
D
Mann
C
C
D000331:Aequorin / Q000494:pharmacology; D000535:Aluminum / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006868:Hydrolysis; D007425:Intracellular Membranes / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010539:Permeability; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D000331:Aequorin; D000535:Aluminum; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005459:Fluorides; D002118:Calcium