Regulation of sodium transport and blood pressure by neuropeptide FF and its receptors in the kidney

Neuropeptide FF (NPFF), an amidated neuropeptide originally isolated from bovine brain, is a pain-modulating peptide with diverse physiological and pathophysiological functions. NPFF and its receptors, NPFFR1 and NPFFR2, are also present in peripheral tissues, including the kidney; NPFF, NPFFR1, and NPFFR2 mRNA and proteins are expressed in mouse and human renal proximal tubules determined by in situ RNA hybridization, immunofluorescence imaging, western blotting, and confirmed by liquid chromatography-tandem mass spectrometry (NPFF, mouse only). In mouse renal proximal tubule cells, NPFF decreased the forskolin-stimulated cAMP production in a concentration (10 -12 -10 -5 M) and time (0-180 min)-dependent manner. NPFF participates in the central and peripheral regulation of blood pressure (BP). The intravenous or renal subcapsular infusion (renal-selective) of NPFF in C57BL/6 mice increased BP, which was prevented by RF-9, an antagonist of NPFF receptors. In C67BL/6 mice fed a high (4%) NaCl diet, the renal subcapsular infusion of Npffr1 or Npffr2 siRNA decreased systolic BP, but urinary sodium excretion was only increased by Npffr2 siRNA. On 4% NaCl diet, the systolic BP of mice with germline deletion of Npffr2 was lower than that of wild-type littermates. In mouse and human renal proximal tubule cells, NPFF decreased intracellular sodium concentration; NPFF (100 nM) decreased the fluorescence lifetime, τ2, using Asante NaTRIUM Green-2 and fluorescence lifetime imaging microscopy. We conclude that renal NPFF, via NPFFR2, positively regulates renal sodium transport and BP. National Institutes of Health (DK119652 and DK134574) and intramural CDRF grant of George Washington University (002655) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.