PROTEIN RESTRICTION SEQUENTIALLY INDUCES NEW UREA TRANSPORT PROCESSESIN RAT INITIAL IMCD

We reported that feeding rats 8% protein for 4 wk induces two new urea transport processes in initial inner medullary collecting ducts (IMCD ); neither is present in rats fed 18% protein. In this study, we measu red the time course of induction of these transporters in perfused ini tial IMCD segments from rats fed 8% protein. Net urea flux was induced after 3 wk, whereas vasopressin-stimulated passive urea permeability (P-urea) was induced after 2 wk. 8-Bromoadenosine 3',5'-cyclic monopho sphate (8-BrcAMP) significantly increased P-urea; adding vasopressin d id not increase P-urea further. In fact, there was no difference in va sopressin-stimulated cAMP production in initial or terminal IMCD segme nts from rats fed 18% or 8% protein, suggesting that the adaptive resp onse was not due to increased cAMP production. Glucagon did not change cAMP production or P-urea. Specificity of the response was suggested because neither aldose reductase nor sorbitol dehydrogenase activity c hanged with feeding 8% protein. Thus 1) in initial IMCD segments, vaso pressin-stimulated P-urea is induced after 2 wk, but net urea flux req uires 3 wk of feeding 8% protein; 2) this adaptation is not solely due to a higher rate of cAMP production; and 3) specificity of the adapti ve response is suggested because activities of enzymes responding to d ecreases in concentrating ability are unchanged. These results suggest that two distinct urea transporters may be involved in the adaptation to a low-protein diet.