Role of enteroendocrine L-cells in Arginine Vasopressin - mediated inhibition of colonic anion secretion
de, Costa Gayan
Alexander, R Todd
Journal of Physiology
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Pais, R., Rievaj, J., Meek, C., de, C. G., Jayamaha, S., Alexander, R. T., Reimann, F., & et al. (2016). Role of enteroendocrine L-cells in Arginine Vasopressin - mediated inhibition of colonic anion secretion. Journal of Physiology, 594 4865-4878. https://doi.org/10.1113/JP272053
Arginine vasopressin (AVP) regulates fluid balance and blood pressure via AVPR2 in kidney and AVPR1A in vascular smooth muscle. Its role in intestinal function has received less attention. We hypothesised that enteroendocrine L-cells producing glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), may be a target of AVP and contribute to the control of fluid balance. Avpr1b expression was assessed by quantitative RT-PCR on FACS-isolated L- and control cells and was enriched in colonic L-cells. AVP stimulated GLP-1 and PYY release from primary cultured murine and human colonic cells and was associated with elevated calcium and cAMP concentrations in L-cells as measured in cultures from GLU-Cre/ROSA26-GCaMP3 and GLU-Epac2camps mice. An antagonist of AVPR1B reduced AVP-triggered hormone secretion from murine and human cells. In Ussing chambers, basolaterally applied AVP reduced colonic anion secretion and this effect was blocked by a specific NPY1R antagonist. In human serum, PYY concentrations were higher in samples with raised osmolality or copeptin (a surrogate marker for AVP). In conclusion, we propose that AVP activates L-cell AVPR1B, causing GLP-1 and PYY secretion. PYY in turn reduces colonic anion secretion through epithelial NPY1R. Our data suggest L-cells are active players in hypothalamic control of intestinal fluid homeostasis, providing a potential link between the regulation of blood volume/pressure/osmolality and blood glucose.
arginine vasopressin, anti-diuretic hormone, enteroendocrine, gastrointestinal, glucagon-like peptide-1 (GLP-1), L-cells, Peptide YY (PYY)
This work was funded by grants from the Wellcome Trust (106262/Z/14/Z, 106263/Z/14/Z), the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/3) and Full4Health (FP7/2011-2015, grant agreement no 266408). Juraj Rievaj was initially supported by an EFSD Albert Renold Travel Fellowship.
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External DOI: https://doi.org/10.1113/JP272053
This record's URL: https://www.repository.cam.ac.uk/handle/1810/254752