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Publication : Angiotensin II Type 1 Receptor-Dependent GLP-1 and PYY Secretion in Mice and Humans.

First Author  Pais R Year  2016
Journal  Endocrinology Volume  157
Issue  10 Pages  3821-3831
PubMed ID  27447725 Mgi Jnum  J:240119
Mgi Id  MGI:5882447 Doi  10.1210/en.2016-1384
Citation  Pais R, et al. (2016) Angiotensin II Type 1 Receptor-Dependent GLP-1 and PYY Secretion in Mice and Humans. Endocrinology 157(10):3821-3831
abstractText  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.
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