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Identifying secondary active solute transport in epithelia.

This Editorial Review analyzes the adequacy of the strategies that are commonly used to establish whether the active transport of a solute does or does not occur by secondary active transport. First, the energetics of noncoupled (passive) diffusion, primary active transport, secondary active transport (coupled diffusion), and solvent drag are briefly described. Second, the kinetics of noncoupled and coupled diffusion processes are discussed. Third, the special difficulties of identifying secondary active solute transport in epithelia are outline. Several factors are described that may obscure or mimic true coupled diffusion. Last, the use of transport inhibitors for identifying coupled diffusion processes is briefly illustrated. The adequacy of the strategies that have been employed to evaluate the role of luminal membrane Na+-H+ exchange in mediating proximal tubular acidification is particularly emphasized. It is concluded that many of the findings apparently supporting a major contribution of Na+-independent, primary active H+ secretion to the proximal tubular acidification process are not necessarily inconsistent with secondary active H+ secretion via Na+-H+ exchange.