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.
Highlights
The prime functions of the gut are the digestion and absorption of ingested food
Angiotensin II (Ang II) interacts with two seven-transmembrane G-protein coupled receptors, AT1 and AT2
In addition to the average ingested fluid volume of ~2.5 litres per day in humans, it has been estimated that 5-10 litres of water are secreted into the gut lumen and re-absorbed to aid intestinal processes [33], necessitating a close link between the gut and systems regulating body fluid and electrolyte homeostasis
Summary
The prime functions of the gut are the digestion and absorption of ingested food These are regulated by intestinal hormones, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), which are co-secreted from enteroendocrine L-cells found predominantly in the ileum and colon [1]. Both hormones underlie the ileal break, slowing gastric emptying when nutrient delivery exceeds the absorptive capacity of the duodenum/jejunum, and control food intake and appetite [2].
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