Heavy metal inhibition of p-aminohippurate transport in flounder renal tissue: sites of HgCl2 action.
p-Aminohippurate (PAH) uptake by teased flounder renal tubules was concentrative, Na-dependent, dependent on aerobic metabolism and inhibited by competitor organic anions and ouabain. Dose-response data for ouabain inhibition of PAH transport and tubule Na,K-adenosine triphosphatase (ATPase) activity were identical. In ouabain-treated tubules, reductions in PAH uptake correlated with alterations in total tissue Na and K even though both were not affected during the first 5 to 10 min of ouabain exposure. No such delay was found with HgCl2 and, as with ouabain, reductions in transport correlated well with alterations in tissue Na and K. Tissue respiration data indicated that low concentrations of HgCl2 rapidly affected the Na,K-ATPase. With higher HgCl2 concentrations, intracellular metabolic sites appeared to be affected. Transport studies with ouabain-poisoned tubules and plasma membrane vesicles indicated that the energetically uncoupled PAH carrier(s) were affected by HgCl2, but carrier sensitivities to Hg were lower than for the Na,K-ATPase. The data indicate that HgCl2 inhibits PAH transport primarily by reducing ion gradients that drive PAH transport. Both inhibition of Na,K-ATPase and increases in membrane permeability to Na and K appear to be involved.
D000618:Aminohippuric Acids / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005399:Fishes / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008627:Mercuric Chloride; D008628:Mercury / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D000618:Aminohippuric Acids; D008627:Mercuric Chloride; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D008628:Mercury; D011188:Potassium; D010130:p-Aminohippuric Acid