title: Postprandial adjustments in renal phosphate excretion do not involve a gut-derived phosphaturic factor.
abstract: What is the central question of this study? Does a previously hypothesized signalling mechanism, believed to detect postprandial increases in intestinal phosphate and that can stimulate the kidneys to rapidly excrete phosphate, operate under physiological conditions? What is the main finding and its importance? Contrary to earlier reports, rapid signalling between the small intestine and kidney mediated by a gut-derived phosphaturic factor in response to a physiological intestinal phosphate load is not supported by the present findings; moreover, hyperphosphataemia and increased parathyroid hormone concentrations are likely to be the underlying factors responsible for the phosphaturia following a supraphysiological intestinal phosphate load. To date, the role of the small intestine in the regulation of postprandial phosphate homeostasis has remained unclear and controversial. Previous studies have proposed the presence of a gut-derived phosphaturic factor that acts independently of changes in plasma phosphate concentration or parathyroid hormone (PTH) concentration; however, these early studies used duodenal luminal phosphate concentrations in the molar range, and therefore, the physiological relevance of this is uncertain. In the present study, we used both in vivo and in vitro approaches to investigate the presence of this putative 'intestinal phosphatonin'. Instillation of 1.3 m phosphate into the duodenum rapidly induced phosphaturia, but in contrast to previous reports, this was associated with significant hyperphosphataemia and elevated PTH concentration; however, there was not the expected decrease in abundance of the renal sodium-phosphate cotransporter NaPi-IIa. Instillation of a physiological (10 mm) phosphate load had no effect on plasma phosphate concentration, PTH concentration or phosphate excretion. Moreover, phosphate uptake by opossum kidney cells was unaffected after incubation with serosal fluid collected from intestinal segments perfused with different concentrations of phosphate. Taken together, these findings do not support the concept of a gut-derived phosphaturic factor that can mediate rapid signalling between the gut and kidney, leading to increased urinary phosphate excretion, as part of normal phosphate homeostasis.
authors.affiliation: Centre for Nephrology, University College London, London, NW3 2PF, UK.
authors.forename: Grace J
authors.initials: GJ
authors.lastname: Lee
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, NW3 2PF, UK.
authors.forename: Lina
authors.initials: L
authors.lastname: Mossa-Al Hashimi
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, NW3 2PF, UK.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Debnam
authors.affiliation: Centre for Nephrology, University College London, London, NW3 2PF, UK.|Department of Neuroscience, Physiology and Pharmacology, University College London, London, NW3 2PF, UK.
authors.forename: Robert J
authors.identifier: 0000-0001-7839-6031
authors.initials: RJ
authors.lastname: Unwin
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, NW3 2PF, UK.
authors.forename: Joanne
authors.identifier: 0000-0002-2677-2477
authors.initials: J
authors.lastname: Marks
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D019518:Postprandial Period / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D027981:Symporters
keywords: phosphatonin; phosphaturia; small intestine