PERITUBULAR ORGANIC CATION-TRANSPORT IN ISOLATED RABBIT PROXIMAL TUBULES

The physiological characteristics of peritubular organic cation transp ort were examined by measuring the transport of the organic cation tet raethylammonium (TEA) in rabbit renal proximal tubule suspensions and isolated nonperfused rabbit renal proximal tubules. Peritubular organi c cation transport in both single 82 segments and suspensions of isola ted renal proximal tubules was found to be a highcapacity, high-affini ty, carrier-mediated process. For tubule suspensions, the maximal capa city of the carrier for TEA (J(max)) and the concentration of TEA at 1 /2 J(max) (K-t) (1.49 +/- 0.21 nmol.min(-1).mg dry wt(-1) and 131 +/- 16 mu M, respectively), did not differ significantly from those measur ed in single 82 segments (J(max), 1.16 +/- 0.075 nmol.min(-1)mg dry wt (-1); K-t, 108 +/- 10 mu M). In addition, the pattern of inhibition of peritubular TEA transport by long-chain n-tetraalkylammonium compound s (n = 1-5) was both qualitatively and quantitatively similar in singl e 82 segments and tubule suspensions, exhibiting an increase in inhibi tory potency with increasing alkyl chain length. For example, in tubul e suspensions, apparent Michaelis constants for inhibition of TEA upta ke ranged from 1.3 mM for tetramethylammonium (TMA) to 0.8 mu M for te trapentylammonium (TPeA). To determine whether these compounds were su bstrates for the peritubular organic cation transporter, their effect on the efflux of [C-14]TEA from tubule suspensions was examined. A con centration of 0.5 mM of the short-chain tetraalkyls TMA or TEA increas ed the efflux of [C-14]TEA (i.e., trans-stimulated) from tubules in su spension. The longer-chain tetraalkyls tetrapropylammonium, tetrabutyl ammonium, and TPeA all decreased the efflux of [C-14]TEA from tubules in suspension; TPeA completely blocked efflux. Thus, in contrast to th e inhibitory potency of these agents, the efficiency of their transpor t by the peritubular organic cation transporter appeared to decrease w ith increasing alkyl chain length.