ABSTRACT
Pathways for p-aminohippurate (PAH) transport across the basolateral membrane of rabbit proximal tubule cells were investigated from studies of [3H] PAH uptake in membrane vesicles isolated by Percoll-density gradient centrifugation. The 10-s uptake of PAH was not significantly different when measured in the absence of cation gradients or in the presence of inwardly directed Na, Li, K or choline gradients that suggests the absence of a mechanism mediating Na-PAH cotransport. A probenicid-sensitive, trans-stimulation of [3H] PAH uptake was observed in the presence of an outward PAH gradient. PAH gradient-driven [3H] PAH uptake was cis-inhibited by glutarate, alpha-ketoglutarate, adipate and sebacate and outward gradients of alpha-ketoglutarate trans-stimulated probenicid-sensitive PAH uptake. A concentrative accumulation of PAH was measured in the presence of an inward Na gradient and the dicarboxylates glutarate or alpha-ketoglutarate. Compared to the absence of a pH gradient, an inside alkaline pH gradient induced an increased PAH uptake both in the presence and absence of CO2/HCO3. Inside-negative and inside-positive voltage differences were observed to stimulate and inhibit alpha-ketoglutarate gradient-driven PAH uptake, respectively. alpha-Ketoglutarate gradient-driven PAH uptake was progressively reduced in the presence of increasing penicillin concentration and an outward gradient of alpha-ketoglutarate induced an increased level of [14C] penicillin uptake. These results suggest the presence of a probenicid-sensitive organic anion exchange mechanism as a pathway for PAH and penicillin transport across the basolateral membrane of rabbit proximal tubule cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Kidney Tubules, Proximal/metabolism , Animals , Cell Membrane/metabolism , Ion Transport , Ketoglutaric Acids/pharmacology , Male , Penicillins/pharmacokinetics , Penicillins/pharmacology , Rabbits , Sodium/metabolism , Substrate Specificity , p-Aminohippuric Acid/pharmacokineticsABSTRACT
Pathways for urate transport across the basolateral membrane of rat proximal tubule cells were investigated using membrane vesicles isolated from rat renal cortex. The presence of an anion exchange mechanism(s) operative in the mode of alpha-keto-glutarate/urate; Cl-/urate and OH-(HCO3-)/urate as well as a mediated conductive mechanism was assessed from tracer flux measurements. In the presence of an inwardly directed Na+ gradient an alpha-ketoglutarate dependent concentrative accumulation of PAH but not urate was observed suggesting an absence of the mediated exchange of alpha-ketoglutarate for urate. The imposition of an outwardly directed Cl- gradient stimulated urate uptake in the absence but not the presence of conditions designed to minimize membrane potential development suggesting an indirect electrostatic coupling of urate uptake to a Cl- gradient-induced diffusion potential. Conditions favoring the development of an inside-positive K+ diffusion potential was observed to induce an inhibitor-sensitive, concentrative accumulation of urate in the absence of Cl-. The stimulation of urate uptake measured in the presence of an inside-alkaline pH gradient was not of sufficient magnitude to suggest the apparent conductive urate uptake was secondary to a membrane voltage induced, inside alkaline pH gradient and the operation of an OH-(HCO3-)/urate exchanger. The evidence obtained from the present investigation suggests rat basolateral membrane urate transport occurs by a mediated, conductive mechanism and is not coupled to Cl-, alpha-ketoglutarate or HCO3-.(ABSTRACT TRUNCATED AT 250 WORDS)
