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Release of endogenous opioids from duodenal enteroendocrine cells requires Trpm5
Zaza Kokrashvili1, Deniliz Rodriguez, Valeriya Yevshayeva
1Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.
Background & Aims:
Enteroendocrine cells, the largest and most diverse population of mammalian endocrine cells, comprise a number of different cell types in the gut mucosa that produce, store, and secrete small molecules, peptides, and/or larger proteins that regulate many aspects of gut physiology. Little is known about less typical endocrine cells in the intestinal mucosa that do not contain secretory granules, such as brush or caveolated cells. We studied a subset of these enteroendocrine cells in duodenum that produce several peptides, including endogenous opioids, and that also express the Trpm5 cation channel.
Methods:
We studied expression patterns of Trpm5 and other molecules by immunohistochemical and enzyme-linked immunosorbent assay analyses of intestinal tissues from transgenic mice that express green fluorescent protein from the Trpm5 promoter, as well as wild-type and Trpm5-null mice.
Results:
We describe a type of enteroendocrine cell in mouse duodenum that is defined by the presence of Trpm5 and that does not contain typical secretory granules yet expresses endogenous opioids (beta-endorphin and Met-enkephalin) and uroguanylin in apical compartments close to the lumen of the gut.
Conclusions:
Solitary chemosensory cells that coexpress beta-endorphin, Met-enkephalin, uroguanylin, and Trpm5 exist in mouse duodenum. These cells are likely to secrete the bioactive peptides into the intestinal lumen in response to dietary factors; release of the opioid peptides requires the Trpm5 ion channel.
Insights
Researchers identified novel enteroendocrine cells in the mouse duodenum that co-express opioid peptides and Trpm5. These cells release peptides into the gut lumen, a process dependent on the Trpm5 ion channel.
Area of Science:
- Gastroenterology
- Endocrinology
- Cell Biology
Background:
- Enteroendocrine cells regulate gut physiology through secreted molecules.
- Less-understood enteroendocrine cells lack secretory granules.
- A specific subset expresses Trpm5 and produces peptides.
Purpose of the Study:
- Characterize a novel enteroendocrine cell type in the duodenum.
- Investigate the role of Trpm5 in these cells.
- Determine the secretory function and regulation of these cells.
Main Methods:
- Immunohistochemistry and ELISA on mouse intestinal tissues.
- Analysis of wild-type, Trpm5-null, and Trpm5-reporter mice.
- Expression pattern analysis of Trpm5 and associated molecules.
Main Results:
- Identified a distinct enteroendocrine cell population in the mouse duodenum defined by Trpm5 expression.
- These cells lack typical secretory granules but contain opioid peptides (beta-endorphin, Met-enkephalin) and uroguanylin.
- Peptides are localized to apical compartments near the gut lumen.
Conclusions:
- Discovered solitary chemosensory cells in the duodenum co-expressing beta-endorphin, Met-enkephalin, uroguanylin, and Trpm5.
- These cells likely secrete bioactive peptides into the intestinal lumen in response to dietary cues.
- Trpm5 ion channel is essential for the release of these opioid peptides.
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