ATP-stimulated tetraethylammonium transport by rabbit renal brush border membrane vesicles.
These studies examined the ability of ATP to stimulate transport of the organic cation tetraethylammonium (TEA) into proximal tubular brush border membrane vesicles. ATP markedly enhanced TEA uptake for 1 h or more to values severalfold above those observed in the absence of ATP. The poorly hydrolyzable analogue of ATP, AMP-PNP (adenyl-5'-yl imidodiphosphate), reduced the effect of ATP but alone did not stimulate TEA uptake. GTP and ITP also stimulated TEA uptake, whereas other nucleotides did not. ATP-stimulated TEA uptake was saturable, temperature-dependent, and markedly reduced by the organic cations amiloride, quinidine, cimetidine, and verapamil, but only modestly reduced by the organic cations N'-methylnicotinamide and choline. Some inhibitors of other transport ATPases, including N-ethylmaleimide, N,N'-dicyclohexylcarbodiimide, and oligomycin, reduced the effect of ATP, whereas ouabain, vanadate, and azide did not. 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid also reduced TEA uptake in the presence of ATP. Vinblastine, but not actinomycin D and colchicine (all inhibitors of P-glycoprotein-mediated transport), reduced TEA uptake. The reduction of TEA transport by amiloride and cimetidine was most consistent with competitive inhibition, whereas the inhibition produced by N-ethylmaleimide and vinblastine evidently was not. ATP also stimulated uptake of N'-methylnicotinamide but not that of vinblastine. These studies have identified a previously unrecognized process by which ATP hydrolysis may directly energize the reabsorption of organic cations from the renal tubule lumen.
McKinney
T D
TD
Department of Medicine, Veterans Affairs Medical Center, Indiana University Medical Center, Indianapolis 46202-5116.
Hosford
M A
MA
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002021:Buffers; D007672:Kidney Cortex / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000378:metabolism; D011817:Rabbits; D013696:Temperature; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D002021:Buffers; D013757:Tetraethylammonium Compounds; D014638:Vanadates; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases