title: Angiotensin II Type 1 Receptor-Dependent GLP-1 and PYY Secretion in Mice and Humans.
abstract: Angiotensin II (Ang II) is the key hormone mediator of the renin angiotensin system, which regulates blood pressure and fluid and electrolyte balance in the body. Here we report that in the colonic epithelium, the Ang II type 1 receptor is highly and exclusively expressed in enteroendocrine L cells, which produce the gut hormones glucagon-like peptide-1 and peptide YY (PYY). Ang II stimulated glucagon-like peptide-1 and PYY release from primary cultures of mouse and human colon, which was antagonized by the specific Ang II type 1 receptor blocker candesartan. Ang II raised intracellular calcium levels in L cells in primary cultures, recorded by live-cell imaging of L cells specifically expressing the fluorescent calcium sensor GCaMP3. In Ussing chamber recordings, Ang II reduced short circuit currents in mouse distal colon preparations, which was antagonized by candesartan or a specific neuropeptide Y1 receptor inhibitor but insensitive to amiloride. We conclude that Ang II stimulates PYY secretion, in turn inhibiting epithelial anion fluxes, thereby reducing net fluid secretion into the colonic lumen. Our findings highlight an important role of colonic L cells in whole-body fluid homeostasis by controlling water loss through the intestine.
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
authors.forename: Ramona
authors.initials: R
authors.lastname: Pais
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
authors.forename: Juraj
authors.initials: J
authors.lastname: Rievaj
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
authors.forename: Pierre
authors.initials: P
authors.lastname: Larraufie
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Gribble
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling; D003106:Colon / Q000502:physiology*; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019894:Peptide YY / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012084:Renin-Angiotensin System; D014882:Water-Electrolyte Balance
chemical_list: D044140:Receptor, Angiotensin, Type 1; D019894:Peptide YY; D000804:Angiotensin II; D052216:Glucagon-Like Peptide 1