Organic substrate effects on and heterogeneity of Necturus proximal tubule function

The effect of organic substrates such as lactate, alanine, glutamine, glutamate, lysine, and butyrate is compared with that of glucose, and the role of tubular heterogeneity is assessed in Necturus proximal tubule. Fluid absorption (Jv) is enhanced 34% by the presence of all substrates together in the tubular lumen. Addition of glucose to the peritubular perfusion fluid does not increase Jv significantly, whereas the other substrates augment Jv by 181%. Transepithelial potential difference (V3) and peritubular membrane potential difference (V1) are unaffected by these organic substrates. Transepithelial chloride to sodium transference number ratios (tCl/tNa) and transepithelial specific resistance (Rm) are higher in the presence of substrates, possibly because of effects on paracellular conductance. Organic solutes could influence fluid absorption by increasing entry of sodium across the luminal cell membrane, by increasing energy supply to the active transport mechanism, or by decreasing paracellular conductance. Early and late straight segments of the proximal tubule do not differ significantly in V3, V1, and transepithelial tCl/tNa. Early convoluted segments have a higher Jv than do late straight proximal segments, but they have a lower transepithelial specific resistance. We have concluded that net fluid absorption and transepithelial ionic conductance correlates with the supply of certain organic solutes and with specific localization along the proximal tubule.