Bethanechol and a G-protein activator, NaF/AlCl3, induce secretory response in Paneth cells of mouse intestine

Satoh, Yuichi; Ishikawa, Katsushi; Oomori, Yukio; Takeda, Shozo; Ono, Kazuyuki

doi:10.1007/bf00319611

Cited by 61 publications

(42 citation statements)

References 49 publications

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“…Thus, ASGP-1 must be added to the repertoire of colonic mucins secreted by these cells. In contrast, mucins are not usually considered to be a product of Paneth cells (Satoh et al, 1992). However, one of the functions of Paneth cells appears to be to secrete proteins which protect against infectious agents (Mallow et al, 1996), a function also ascribed to mucins (Patton et al, 1995).…”

Section: Discussionmentioning

confidence: 94%

Expression and localization of Muc4/sialomucin complex (SMC) in the adult and developing rat intestine: Implications for Muc4/SMC function

Rong

Rossi

Zhang

et al. 2004

Journal Cellular Physiology

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Muc4/sialomucin complex (SMC) is a high molecular mass heterodimeric membrane mucin, encoded by a single gene, and originally discovered in a highly metastatic ascites rat mammary adenocarcinoma. Subsequent studies have shown that it is a prominent component of many accessible and vulnerable epithelia, including the gastrointestinal tract. Immunoblot and immunofluorescence analyses demonstrated that Muc4/SMC expression in the rat small intestine increases from proximal to distal regions and is located predominantly in cells at the base of the crypts. These cells were postulated to be Paneth cells, based on their location, morphology, and secretory granule content. Immunohistochemistry indicated the presence of Muc4/SMC in these granules. Muc4/SMC expression was higher in the rat colon than small intestine and was abundantly present in colonic goblet cells, but not in goblet cells in the small intestine. Immunohistochemistry also suggested the presence of MUC4 in human colonic goblet cells. Biochemical analyses indicated that rat colonic Muc4/SMC is primarily the soluble form of the membrane mucin. Analyses of Muc4/SMC during development of the rat gastrointestinal tract showed its appearance at embryonic day 14 of the esophagus and at day 15 at the surface of the undifferentiated stratified epithelium at the gastroduodenal junction, then later at cell surfaces in the more distal regions of the differentiated epithelium of the small intestine, culminating in expression as an intracellular form in the crypts of the small intestine at about day 21. Limited expression in the colon was observed during development before birth at cell surfaces, with expression as an intracellular form in the goblet cells arising during the second week after birth. These results suggest that membrane mucin Muc4/SMC serves different functions during development of the intestine in the rat, but is primarily a secreted product in the adult animal.

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Section: Discussionmentioning

confidence: 94%

Expression and localization of Muc4/sialomucin complex (SMC) in the adult and developing rat intestine: Implications for Muc4/SMC function

Rong

Rossi

Zhang

et al. 2004

Journal Cellular Physiology

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“…However, PCs conceivably also respond to the presence of macromolecules per se, possibly through an osmoreceptor. A third type of PC secretion, possibly linked to parasympathetic autonomic nervous system activity, follows G protein-mediated cholinergic stimulation [82]. PCs secrete in response to cholinergic agonists, including bethanechol [71,82], pilocarpine [83,84], and carbamylcholine [85,88].…”

Section: Pcs Release Their Numerous Granules Upon Microbial Hormonalmentioning

confidence: 99%

The multifaceted Paneth cell

Porter

Bevins

Ghosh

et al. 2002

Cellular and Molecular Life Sciences (CMLS)

361

277

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Paneth cells (PCs) were described over a century ago as granulated cells located at the base of small intestinal crypts, the 'crypts of Lieberkühn.' Various histochemical staining procedures were developed that identified PCs based on their distinctive granule-staining pattern. Early on, PCs were proposed to perform a specialized function other than absorption of digested nutrients, the predominant task of the small intestinal epithelium. Since then, many constituents of the PC granules have been biochemically characterized. The presence of various granule-associated antimicrobial substances and their release upon microbial challenge suggest that PCs function as specialized defense cells in the small intestine. Altered resistance to microbial infection in animal models with disrupted or augmented PC function provides further support for the host defense role of PCs. Other PC components suggest that PCs may also participate in the regulation of lumenal ionic composition, crypt development, digestion, and intestinal inflammation.

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“…The secretory responses occur within minutes of exposure to soluble bacterial antigens or to carbamyl choline and are dose-dependent, suggesting a receptor-mediated process (10). In mouse small intestinal crypts stimulated with carbamyl choline, the cytosolic calcium dynamics change only in Paneth cells in a biphasic pattern consistent with mobilization of intracellular Ca 2ϩ stores followed by influx of extracellular Ca 2ϩ (14,15). These observations led to the hypothesis that Paneth cell secretion in response to bacterial stimuli may be modulated by a cationselective channel that could regulate the influx of extracellular Ca 2ϩ .…”

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confidence: 97%

Modulation of Mouse Paneth Cell α-Defensin Secretion by mIKCa1, a Ca2+-activated, Intermediate Conductance Potassium Channel

Ayabe¹,

Wulff²,

Darmoul³

et al. 2002

Journal of Biological Chemistry

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Immunol. 1, 113-138). We now report that the Ca 2؉ -activated K ؉ channel mIKCa1 modulates mouse Paneth cell secretion. mIKCa1 cDNA clones identified in a mouse small intestinal crypt library by hybridization to human IKCa1 cDNA probes were isolated, and DNA sequence analysis showed that they were identical to mIKCa1 cDNAs isolated from erythroid cells and liver. The genomic organization was found to be conserved between mouse and human IKCa1 as shown by comparisons of the respective cDNA and genomic sequences. Reverse transcriptase-PCR experiments using nested primers amplified mIKCa1 from the lower half of bisected crypts and from single Paneth cells, but not from the upper half of bisected crypts, villus epithelium, or undifferentiated crypt epithelial cells, suggesting a lineage-specific role for mIKCa1 in mouse small bowel epithelium. The cloned mIKCa1 channel was calcium-activated and was blocked by ten structurally diverse peptide and nonpeptide inhibitors with potencies spanning 9 orders of magnitude and indistinguishable from that of the human homologue. Consistent with channel blockade, charybdotoxin, clotrimazole, and the highly selective IKCa1 inhibitors, TRAM-34 and TRAM-39, inhibited (ϳ50%) Paneth cell secretion stimulated by bacteria or bacterial lipopolysaccharide, measured both as bactericidal activity and secreted cryptdin protein, but the inactive analog, TRAM-7, did not block secretion. These results demonstrate that mIKCa1 is modulator of Paneth cell ␣-defensin secretion and disclose an involvement in mucosal defense of the intestinal epithelium against ingested bacterial pathogens.

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Bethanechol and a G-protein activator, NaF/AlCl3, induce secretory response in Paneth cells of mouse intestine

Cited by 61 publications

References 49 publications

Expression and localization of Muc4/sialomucin complex (SMC) in the adult and developing rat intestine: Implications for Muc4/SMC function

Expression and localization of Muc4/sialomucin complex (SMC) in the adult and developing rat intestine: Implications for Muc4/SMC function

The multifaceted Paneth cell

Modulation of Mouse Paneth Cell α-Defensin Secretion by mIKCa1, a Ca2+-activated, Intermediate Conductance Potassium Channel

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