Release of endogenous opioids from duodenal enteroendocrine cells requires Trpm5.
OBJECTIVE
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.
Kokrashvili
Zaza
Z
Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.
Rodriguez
Deniliz
D
Yevshayeva
Valeriya
V
Zhou
Hang
H
Margolskee
Robert F
RF
Mosinger
Bedrich
B
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002478:Cells, Cultured; D004386:Duodenum / Q000166:cytology / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D018847:Opioid Peptides / Q000378:metabolism*; D012680:Sensitivity and Specificity; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D001615:beta-Endorphin / Q000378:metabolism
D018847:Opioid Peptides; D050053:TRPM Cation Channels; C404409:TRPM5 protein, human; D004744:Enkephalin, Methionine; D001615:beta-Endorphin