Inhibition of renal Na+/H+ exchange in cadmium-intoxicated rats.
Chronic exposure to cadmium (Cd) results in bicarbonaturia, leading to metabolic acidosis. To elucidate the mechanism(s) by which renal bicarbonate reabsorption is inhibited, we investigated changes in renal transporters and enzymes associated with bicarbonate reabsorption in Cd-intoxicated rats. Cd intoxication was induced by subcutaneous injections of CdCl(2) (2 mg Cd/kg per day) for 3 weeks. Cd intoxication resulted in a significant reduction in V(max) of Na(+)/H(+) antiport with no changes in K(Na) in the renal cortical brush-border membrane vesicles (BBMV). Western blotting of BBM proteins and indirect immunohistochemistry in renal tissue sections, using an antibody against Na(+)/H(+) exchange-3 (NHE3), showed a diminished expression of NHE3 protein in the BBM. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that NHE3 mRNA expression was reduced in the renal cortex. The activity of carbonic anhydrase IV (CA IV) in BBM was not changed. The protein abundance of Na(+)-HCO(3)(-) cotransporter-1 (NBC1) in whole kidney membrane fractions was slightly attenuated, whereas that of the Na(+)-K(+)-ATPase alpha-subunit was markedly elevated in Cd-intoxicated animals. These results indicate that Cd intoxication impairs NHE3 expression in the proximal tubule, thereby reducing the capacity for bicarbonate reabsorption, leading to bicarbonaturia in an intact animal.
Ahn
Do Whan
DW
Department of Physiology, Kosin University College of Medicine, Busan 602-702, South Korea.
Chung
Jin Mo
JM
Kim
Jee Yeun
JY
Kim
Kyoung Ryong
KR
Park
Yang Saeng
YS
D000818:Animals; D002104:Cadmium / Q000032:analysis / Q000633:toxicity*; D030741:Carbonic Anhydrase IV / Q000378:metabolism; D007672:Kidney Cortex / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D012333:RNA, Messenger; C422004:Slc4a4 protein, rat; C000613387:Slc9a3 protein, rat; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D002104:Cadmium; D030741:Carbonic Anhydrase IV; D000254:Sodium-Potassium-Exchanging ATPase