Evidence for a functional intestinal‐renal axis for arginine synthesis in the neonatal pig (258.2)

Abstract

Endogenous arginine (Arg) synthesis is a complex multiorgan process, in which citrulline (Cit) made in the gut is converted into Arg in the kidney, by what is known as the intestinal‐renal axis. In neonates, since the enzymes required to convert Cit into Arg are present in the gut, the prevailing dogma is that this axis is not functional and that Arg, but not Cit, is exported by the gut. Paradoxically, plasma Cit is also used as a marker for gut health and development in the neonate. We have determined Cit and Arg interorgan transactions (µmol•kg‐1•h‐1) in multi‐catheterized, anesthetized neonatal pigs (6‐10 d) using tracers and enzyme localization by immunohistochemistry. The gut released Cit (48±12) and Arg (41±12). Only a small fraction (4±1) of Arg was synthesized from circulating Cit. Because there was no direct utilization of ornithine for Arg synthesis, it is likely that the rest was from proteolysis. Due to enteral Arg uptake (27 ±12) the net Arg balance across the gut was not different from zero. The kidney took up Cit (37±4) and released Arg (28±3). Approximately 50% of the Arg released by the kidney originated from circulating Cit (13±3). The uptake of Arg by kidney (19±7) reduced the net output of renal Arg. Our results in neonatal pigs demonstrate a substantial Cit flux that can be explained by the lack of co‐localization of the enzymes for Cit and Arg synthesis in the gut, and the conversion of plasma Cit into Arg by the kidney.Grant Funding Source: Supported by USDA/ARS Cooperative Agreement No 58‐6250‐6‐001