Stimulation of basolateral Na(+)-HCO3- cotransporter by angiotensin II in rabbit renal cortex.
Angiotensin (ANG) II is now recognized as a powerful direct controller of Na+ reabsorption in the proximal convoluted tubule, a property that predominantly reflects stimulation of the transepithelial NaHCO3 flux. Numerous studies have established that this effect of ANG II represents stimulation of the apical Na+/H+ exchanger, but a single microperfusion study has also suggested direct stimulation of the basolateral Na(+)-HCO3- cotransporter. We have carried out studies in basolateral membrane vesicles from rabbit renal cortex to examine directly whether ANG II exerts an independent effect on the Na(+)-HCO3- cotransporter. Preincubation of vesicles with ANG II (10(-11) to 10(-9) M) for 15 min enhanced the activity of the cotransporter, the greatest effect occurring at 10(-11) M (41 +/- 1.1%, P < 0.005). This stimulation reflected an increase in the maximal enzyme reaction velocity of the cotransporter but no change in the Michaelis constant for Na+. ANG II had no effect on Na(+)-dependent succinate transport. ANG I (10(-9) M) and ANG III (10(-10) M) also stimulated the Na(+)-HCO3- cotransporter, and captopril (10(-4) M) attenuated the ANG I stimulation by 68 +/- 3.5% (P < 0.01) but not that of ANG II and III. Saralasin (10(-11) to 10(-8) M) by itself behaved as an agonist, and its stimulation was additive to that by ANG II. The nonpeptide ANG II receptor antagonist, losartan potassium (10(-6) M), and the disulfide-reducing agent, dithiothreitol (10 mM), each by itself had no effect on the cotransporter but each markedly attenuated the ANG II effect (by 77 +/- 1.4%, P < 0.01 and 74 +/- 1.6%, P < 0.005, respectively) in accord with the view that the basolateral receptor belongs to subtype 1. These results identify physiological concentrations of ANG II as a potent, direct, and specific stimulator of the basolateral Na(+)-HCO3- cotransporter.
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts.
S
S
Eiam-Ong
S A
SA
Hilden
C A
CA
Johns
N E
NE
Madias
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000809:Angiotensins / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000378:metabolism; D009994:Osmolar Concentration; D011817:Rabbits; D012504:Saralasin / Q000494:pharmacology; D027982:Sodium-Bicarbonate Symporters; D017923:Sodium-Hydrogen Exchangers
D000809:Angiotensins; D002352:Carrier Proteins; D027982:Sodium-Bicarbonate Symporters; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; D002216:Captopril; D012504:Saralasin