Intestinal Response to Acute Intragastric and Intravenous Administration of Phosphate in Rats.

ABSTRACT

BACKGROUND/AIMS: Phosphate (Pi) homeostasis is controlled by the intestine and kidneys whose capacities to transport Pi are under endocrine control. Several studies point to intestinal absorption as a therapeutic target to modulate Pi homeostasis. The small intestine is responsible for almost all Pi absorption in the gut, a process involving Na+-dependent and independent mechanisms. Three Na+-dependent Pi cotransporters have been described in the gastrointestinal tract NaPi-IIb (a SLC34 member) and Pit-1 and Pit-2 (SLC20 transporters). We recently analysed the acute hormonal and renal response to intragastric (i.g) and intravenous (i.v) Pi-loading. This study demonstrated that the kidney quickly adapts to Pi-loading, with changes manifesting earlier in the i.v than i.g intervention. The aim of this work was to extend the previous studies in order to investigate the acute adaptation of intestinal transport of Pi and expression of intestinal Na+/Pi-cotransporters in response to acute Pi-loading. METHODS: Duodenal and jejunal mucosa was collected 40 minutes and/or 4 hours after administration (i.g and i.v) of either NaCl or Pi to anaesthetized rats. Uptakes of Pi and protein expression of Na+/Pi cotransporters were measured in brush border membrane vesicles (BBMV); the cotransporters' mRNA abundance was quantified by real-time PCR in total RNA extracted from whole mucosa. RESULTS: Pi-loading did not modify transport of Pi in duodenal and jejunal BBMV 4 hours after treatment. Administration of Pi did not alter either the intestinal expression of NaPi-IIb and Pit-2 mRNAs, whereas Pit-1 mRNA expression was only regulated (diminished) in duodenum collected 4 hours after i.g Pi-loading. NaPi-IIb protein expression was decreased in duodenum 4 hours upon i.v Pi infusion, whereas the duodenal and jejunal abundance of the cotransporter was unaffected by i.g administration of Pi. CONCLUSION: Together, these data suggest that the intestine responds acutely to Pi-loading, though this response seems slower than the renal adaptation.