Substrate-induced modulation of ATP turnover in dog and rabbit proximal tubules.
In dog proximal tubules in suspension, the addition of glucose increased significantly the ouabain-sensitive fraction of respiration, a response suppressed by phlorizin. The addition of alpha-methyl-D-glucoside (alpha-MG) had a modest effect and 3-O-methyl-D-glucoside (3-O-MG) had no effect. The different stimulation of the Na+,K(+)-ATPase activity elicited for each hexose could be explained by a different increment of net transepithelial flux of sodium induced by the sodium: hexose cotransport. This flux is a direct function of the transport characteristics of both luminal and antiluminal membranes of proximal cells for these sugars: glucose is rapidly transported by both membranes (allowing a large transepithelial flux of glucose: sodium) while alpha-MG is poorly transported by the basolateral, and 3-O-MG by the luminal, membrane of the dog proximal tubule (allowing a small transepithelial flux of hexoses and sodium). However the overall tubular respiration of dog proximal tubules was not increased by glucose addition because the increment in the ouabain-sensitive fraction was accompanied by a reciprocal decrement in an ouabain-insensitive but oligomycin- or N',N' dicyclohexylcarbodiimide (DCCD)-sensitive (or in the bafilomycin-sensitive) component of respiration. This component reflects the activity of a large BBM-bound H(+)-ATPase found in this species. The intracellular pH of dog proximal tubules in suspension was measured using the proton-sensitive fluorescent probe 2',7'-bis-2-(carboxyethyl)-5, (and 6)-carboxyfluorescein. Glucose application significantly alkalinized the cells. In contrast, other substrates such as lactate or acetate simultaneously acidified the cells and increased the ouabain-insensitive phosphorylative respiration of dog tubules. These observations suggest that a modulation of the activities of both the sodium and most probably the proton pump is elicited by substrate availability in suspensions of proximal tubules.
Noël
J
J
Université de Montréal, Départements de Medecine et de Physiologie, Hôpital Notre-Dame de Montréal, Canada.
Tejedor
A
A
Vinay
P
P
Laprade
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D004285:Dogs; D005947:Glucose / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000201:enzymology / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013379:Substrate Specificity
D006601:Hexoses; D009840:Oligomycins; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose