Abstract
Tetraethylammonium (TEA) and amantadine are two organic cations that are secreted by the kidney. It appears that each cation may characterize distinct renal tubule organic cation transport pathways. To test this hypothesis, we investigated the renal proximal and distal tubule energy-dependent transport properties of TEA and amantadine. Isolated tubules were incubated at 25°C in bicarbonate buffer (Krebs-Henseleit solution) and nonbicarbonate buffer (Cross-Taggart) with varying concentrations of [14C]TEA or [3H]amantadine to determine initial rates of energy-dependent uptake of TEA and amantadine, respectively. The uptake of TEA could best be described by two transport sites, a high-affinity site and a lower affinity site. TEA uptake was not influenced by the presence of bicarbonate. Consistent with our previously reported data, amantadine uptake could also be described by two transport sites, a high-affinity-capacity site that is bicarbonate-dependent and a lower-affinity-capacity transport site that is bicarbonate-independent. The renal tubule uptake of amantadine into proximal and distal tubules, in Krebs-Henseleit solution or Cross-Taggart buffers, was not inhibited by 10 to 1000 μM of TEA. However, tubule accumulation of TEA could be inhibited (>90%) by amantadine in proximal and distal tubules in Krebs-Henseleit solution and Cross-Taggart buffers. In proximal tubules, N1-methylnicotinamide was not able to inhibit amantadine uptake but it reduced TEA uptake by 60 to 70% at similar concentrations. These data support the existence of multiple renal tubule organic cation transporters that have different substrate affinity and controlling mechanisms. It is also apparent that amantadine characterizes organic cation transporters that are distinct from those characterized by TEA.
Footnotes
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Send reprint requests to: Daniel S. Sitar, Ph.D., Clinical Pharmacology Section, University of Manitoba, A206-770 Bannatyne Ave., Winnipeg, Manitoba, Canada R3E 0W3. E-mail:sitar{at}ms.umanitoba.ca
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↵1 This study was funded by Grants MA-11664 and MT-14710 from the Medical Research Council of Canada.
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↵2 Recipient of a Manitoba Health Research Council Studentship.
- Abbreviations:
- CT
- Cross-Taggart
- KHS
- Krebs-Henseleit solution
- TEA
- tetraethylammonium
- rOCT
- rat organic cation transporter
- NMN
- N1-methylnicotinamide
- Received December 4, 1998.
- Accepted March 17, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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