Effects of thiazide on the expression of TRPV5, calbindin-D28K, and sodium transporters in hypercalciuric rats.
TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D(28K), and several sodium transporters in hypercalciuric rats. Sprague-Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2. To quantitate the expression of TRPV5, calbindin-D(28K), and sodium transporters, western blotting was performed. In both experiments, HCTZ significantly decreased urinary calcium excretion. TRPV5 protein abundance decreased in all hypercalciuric rats, and restored by HCTZ in both high salt with HCTZ and high Ca with HCTZ group. Calbindin-D(28K) protein abundance increased in the high salt and high salt with HCTZ groups, but did not differ among groups in experiment 2. Protein abundance of NHE3 and NKCC2 decreased in all hypercalciuric rats, and were restored by HCTZ in only high Ca-induced hypercalciuric rats. In summary, protein abundance of TRPV5, NHE3, and NKCC2 decreased in all hypercalciuric rats. The hypocalciuric effect of HCTZ is associated with increased protein abundance of TRPV5 in high salt or calcium diet-induced hypercalciuric rats.
Jang
Hye Ryoun
HR
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kim
Sejoong
S
Heo
Nam Ju
NJ
Lee
Jeong Hwan
JH
Kim
Hyo Sang
HS
Nielsen
Søren
S
Jeon
Un Sil
US
Oh
Yun Kyu
YK
Na
Ki Young
KY
Joo
Kwon Wook
KW
Han
Jin Suk
JS
D000818:Animals; D001692:Biological Transport; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000652:urine; D015220:Calcium Channels / Q000737:chemistry; D006852:Hydrochlorothiazide / Q000494:pharmacology; D053565:Hypercalciuria / Q000628:therapy*; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis*; D012964:Sodium / Q000378:metabolism*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D050916:TRPV Cation Channels / Q000096:biosynthesis* / Q000737:chemistry; D049971:Thiazides / Q000494:pharmacology*
C576498:CALB1 protein, human; C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels; D064030:S100 Calcium Binding Protein G; C578714:SLC12A1 protein, human; C000613385:SLC9A3 protein, human; C578716:Slc12a1 protein, rat; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D050916:TRPV Cation Channels; C492239:TRPV5 protein, human; C492241:TRPV5 protein, rat; D049971:Thiazides; D006852:Hydrochlorothiazide; D012964:Sodium; D002118:Calcium