Effects of carbonic anhydrase inhibitors on basolateral base transport of rabbit proximal straight tubule.
The effect of carbonic anhydrase inhibitors on basolateral base transport was examined in rabbit proximal straight tubules (S2 segment) perfused in vitro by double-barreled pH microelectrodes. Bath HCO3- reduction or Na+ removal induced an initial basolateral voltage (Vbl) depolarization followed by a late-phase depolarization. Administration of 1 mM acetazolamide (ACTZ) to the bath fluid caused a small inhibition of the initial depolarization, and a larger inhibition of the late phase depolarization. Bath HCO3- reduction decreased intracellular pH (pHi), and this pHi decrease was attenuated by ACTZ. Bath Na+ removal also decreased pHi, and this pHi decrease was completely blocked by ACTZ. However, a slow pHi decrease was observed in response to bath Na+ removal when the bath fluid contained ACTZ and the luminal fluid contained 4 mM amiloride. The addition of ACTZ or ethoxyzolamide to the bath caused a rapid Vbl hyperpolarization and pHi increase. These results demonstrate that carbonic anhydrase inhibitors inhibit basolateral Na(HCO3)n transport in intact rabbit proximal tubule cells (S2). The data suggest that at least one of the base species transported by the transporter is HCO3-, and cytosolic carbonic anhydrase is important in converting intracellular OH- to HCO3-.
Sasaki
S
S
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Marumo
F
F
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002794:Choline / Q000494:pharmacology; D005016:Ethoxzolamide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D013844:Thiazoles; D012964:Sodium; D002794:Choline; D000086:Acetazolamide; D005016:Ethoxzolamide