Basolateral tetraethylammonium transport in intact tubules: Specificity and trans-stimulation

To examine the specificity of prox imal renal basolateral organic cation transport, the effects of unlabeled organic cation substrates in the bathing medium on the rate of uptake of [¹⁴C]tetraethylammonium ([¹⁴C]TEA) by intact nonperfused proximal tubules and isolated basolateral membrane vesicles (BLMV) from rabbit kidneys were explored. The pattern of inhibition of transport by a battery of unlabeled organic cations was similar in intact tubules and BLMV. To determine if trans-stimulation could be demonstrated across the basolateral membrane of intact tubules, the effects of preloading tubules with unlabeled substrates on the rate of uptake of [¹⁴C]TEA and the effects of unlabeled substrates in the bathing medium on the rate of efflux of [¹⁴C]TEA from tubules preloaded with this labeled substrate were examined. Trans-stimulation was clearly demonstrated for the first time in intact tubules. However, of the compounds that significantly inhibited [¹⁴C]TEA uptake (TEA, amiloride, tetrapropylammonium, mepiperphenidol, isopropyl pyridinium, and choline), only TEA itself and choline produced a trans-stimulation of [¹⁴C]TEA uptake. Moreover, choline appeared to be at least as effective as TEA itself as a counter ion for TEA transport. Such trans-stimulation could play a physiological role in the net reabsorption of choline and the net secretion of most other organic cations.