Protein restriction sequentially induces new urea transport processes in rat initial IMCD

Abstract

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 measured the time course of induction of these transporters in perfused initial 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 monophosphate (8-BrcAMP) significantly increased P(urea)); adding vasopressin did not increase P(urea) further. In fact, there was no difference in vasopressin-stimulated cAMP production in initial or terminal IMCD segments from rats fed 18% or 8% protein, suggesting that the adaptive response 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 changed with feeding 8% protein. Thus 1) in initial IMCD segments, vasopressin-stimulated P(urea) is induced after 2 wk, but net urea flux requires 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 adaptive response is suggested because activities of enzymes responding to decreases in concentrating ability are unchanged. These results suggest that two distinct urea transporters may be involved in the adaptation to a low-protein diet.

A comparison of nitrogen utilization and urea metabolism between Tibetan and fine-wool sheep1

“…Changes in renal urea N reabsorption in relation to the N content of the diet were consistent with existing reports (Tebot et al, 1998;Marini et al, 2004); renal tubular load of urea N increased, whereas the proportion of urea N reabsorbed decreased, with increasing dietary N. Schmidt-Nielsen et al (1958) reported that urea reabsorption rose when animals were fed low N diets, and Isozaki et al (1994) characterized the involvement of the kidney in this phenomenon in rats.…”

Active sodium-urea counter-transport is inducible in the basolateral membrane of rat renal initial inner medullary collecting ducts.

“…Schmidt-Nielsen and colleagues first demonstrated the existence of active urea reabsorption which is coupled to sodium reabsorption in the kidney of the spiny dogfish, Squalus acanthias (16). We showed that urea is actively reabsorbed via a secondary active, sodium-coupled cotransport process in the rat initial IMCD (IMCD 1 ) from rats fed a low-protein diet for 3 wk (9)(10)(11). We also showed that urea is actively secreted via a secondary active, sodium-coupled countertransport process in the deepest portion of the rat terminal IMCD, the IMCD 3 , but not in the middle third of the IMCD, the IMCD 2 , nor in the initial IMCD of rats fed a normal diet (12).…”

“…In addition to facilitated urea transport, there is evidence for active urea transport process(es) in the kidney of rat (9)(10)(11)(12), rabbit (13), dog (14,15), spiny dogfish (16), and human (17). Schmidt-Nielsen and colleagues first demonstrated the existence of active urea reabsorption which is coupled to sodium reabsorption in the kidney of the spiny dogfish, Squalus acanthias (16).…”

Limits of adaptation to high dietary protein intakes

“…The last decade has seen the closer characterisation of a family of aquaporins, which have the general property of moving water and urea across membranes. The identi®ca-tion of a urea transporter in the kidney of the rat which is responsive to dietary protein intake (Isozaki et al, 1994;Smith et al, 1995), the demonstration of a transporter which is speci®cally located in the renal collecting duct and the colon (You et al, 1993), and the ®nding of similar capabilities in the human colon (Ritzhaupt et al, 1998) opens the opportunity for a co-ordinated response. It is possible that on a low-protein diet, enhanced retention of urea in the kidney is matched by an enhanced capacity to move urea into the colon where the nitrogen can be salvaged through bacterial activity.…”