Muscarinic Regulation of Somatostatin Release from Primary Cultures of Human Antral Epithelial Cells

Buchan, A.M.J.; MacLeod, MB; Meloche, R. M.; Kwok, Yin Nam

doi:10.1159/000138871

Cited by 18 publications

(6 citation statements)

References 16 publications

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“…The responses reported here are in keeping with the data on somatostatin release from canine fundic D-cells [30,37]. In contrast, muscarinic receptors are stimulatory to antral D-cells [41], probably reflecting a specific difference in function. The current study confirmed the inhibitory actions of both the somatostatin-analogue octreotide and muscarinic agonist carbachol against somatostatin release.…”

Section: Discussionsupporting

confidence: 86%

Regulation of amylin release from cultured rabbit gastric fundic mucosal cells

Beales

Calam

2003

BMC Physiol

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BackgroundAmylin (islet amyloid polypeptide) is a hormone with suggested roles in the regulation of glucose homeostasis, gastric motor and secretory function and gastroprotection. In the gastric mucosa amylin is found co-localised with somatostatin in D-cells. The factors regulating gastric amylin release are unknown. In this study we have investigated the regulation of amylin release from gastric mucosal cells in primary culture. Rabbit fundic mucosal cells enriched for D-cells by counterflow elutriation were cultured for 40 hours. Amylin and somatostatin release over 2 hours in response to agonists were assessed.ResultsAmylin release was significantly enhanced by activation of protein kinase C with phorbol-12-myristate-13-acetate, adenylate cyclase with forskolin and elevation of intracellular calcium with A23187. Cholecystokinin (CCK), epinephrine and glucagon-like peptide-1 (GLP-1) each stimulated amylin release in a dose-dependent manner. Maximal CCK-stimulated release was greater than either epinephrine or GLP-1, even when the effects of the latter two were enhanced by isobutylmethylxanthine. Stimulated amylin release was significantly inhibited by carbachol (by 51–59%) and octreotide (by 33–42%). Somatostatin release paralleled that of amylin.ConclusionsThe cultured D-cell model provides a means of studying amylin release. Amylin secretion is stimulated by receptor-dependent and -independent activation of Ca2+/protein kinase C and adenylate cyclase pathways. Inhibition involves activation of muscarinic receptors and auto-regulation by somatostatin.

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Section: Discussionsupporting

confidence: 86%

Regulation of amylin release from cultured rabbit gastric fundic mucosal cells

Beales

Calam

2003

BMC Physiol

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“…This suggested that gastric SST secretion is regulated by a combination of inhibitory and stimulatory muscarinic receptors. This will clarify the mixed findings obtained using the corpus-fundus and the antrum fractions (17,19). While the G␣i-coupled M4receptor is highly enriched (by more than 20 000-fold) in the gastric SST cells, the stimulatory M3 receptor is expressed at similarly high levels without any enrichment.…”

Section: The M3 and M4 Muscarinic Acetylcholine Receptors Have Opposimentioning

confidence: 73%

“…However, activation of muscarinic receptors in stomach cultures has also been observed to stimulate SST release (17). This was attributed to differences between the regions of the stomach being assayed, the antrum and the corpusfundus (17,19,22), however, the results were difficult to interpret also due to interspecies variations. However, by using pertussis toxin to block G␣i signaling, Chiba and coworkers observed a shift in SST response to acetylcholine from inhibition to stimulation of SST release (19).…”

Section: The M3 and M4 Muscarinic Acetylcholine Receptors Have Opposimentioning

confidence: 99%

“…Several signaling molecules, including neurotransmitters (17)(18)(19)(20)(21)(22), peptide hormones (23)(24)(25)(26)(27), neuropeptides (28 -32) and metabolites have been shown to regulate gastric SST release (33). Several signaling molecules, including neurotransmitters (17)(18)(19)(20)(21)(22), peptide hormones (23)(24)(25)(26)(27), neuropeptides (28 -32) and metabolites have been shown to regulate gastric SST release (33).…”

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confidence: 99%

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Transcriptional and Functional Characterization of the G Protein-Coupled Receptor Repertoire of Gastric Somatostatin Cells

et al. 2015

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In the stomach, somatostatin (SST) acts as a general paracrine negative regulator of exocrine secretion of gastric acid and pepsinogen and endocrine secretion of gastrin, ghrelin, and histamine. Using reporter mice expressing red fluorescent protein (RFP) under control of the SST promotor, we have characterized the G protein-coupled receptors expressed in gastric Sst-RFP-positive cells and probed their effects on SST secretion in primary cell cultures. Surprisingly, besides SST, amylin and PYY were also highly enriched in the SST cells. Several receptors found to regulate SST secretion were highly expressed and/or enriched. 1) The metabolite receptors calcium-sensing receptor and free fatty acid receptor 4 (GPR120) functioned as positive and negative regulators, respectively. 2) Among the neurotransmitter receptors, adrenergic receptors α1a, α2a, α2b, and β1 were all highly expressed, with norepinephrine and isoproterenol acting as positive regulators. The muscarinic receptor M3 acted as a positive regulator, whereas M4 was conceivably a negative regulator. 3) Of the hormone receptors, the GLP-1 and GIP receptors, CCKb (stimulated by both CCK and gastrin) and surprisingly the melanocortin MC1 receptor were all positive regulators. 4) The neuropeptide receptors for calcitonin gene-related peptide, adrenomedullin, and vasoactive intestinal peptide acted as positive regulators, no effect was observed using galanin and nociceptin although transcripts for the corresponding receptors appeared highly expressed. 5) The SST receptors 1 and 2 functioned in an autocrine negative feedback loop. Thus, the article provides a comprehensive map of receptors through which SST secretion is regulated by hormones, neurotransmitters, neuropeptides and metabolites that act directly on the SST cells in the gastric mucosa.

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“…In rat pancreatic islets, cholinergic agonists stimulated insulin and glucagon secretion after binding to M3-subtype receptors (37). I' d134 l No 5 Similar results were registered in canine primary antral Dcells (38) and in the gastrin-producing cell line B6 RIN (39), with carbachol stimulating the secretion of somatostatin and gastrin, respectively. These results favor a preponderant role of M3-subtype receptors in the stimulation of digestive peptide secretion by cholinergic agonists.…”

Section: Discussionmentioning

confidence: 63%

Stimulation of glucagon-like peptide-1 secretion by muscarinic agonist in a murine intestinal endocrine cell line.

Abello

Bosshard

et al. 1994

Endocrinology

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Studies on the cholinergic regulation of intestinal L-cells have been focused on the release of enteroglucagon, but the signal transduction pathways were not defined. These were here investigated by using as index the release of immunoreactive glucagon-like peptide-1 (GLP-1) from the endocrine cell line STC-1, that has been shown to contain proglucagon mRNA transcripts. Abundant GLP-1 immunoreactivity was revealed in STC-1 cells at immunocytochemistry and by RIA. The cell content was 4927 +/- 689 pg/10(6) cells, as measured with antiserum 199D that recognizes specifically the C-terminal amidated forms of GLP-1. The secretion of GLP-1 over a 2-h incubation period amounted to 1.4 +/- 0.3% of the total GLP-1 cell content and was significantly increased by 10 microM forskolin and 100 nM 12-O-tetradecanoylphorbol 13-acetate to 206% and 574% of control values, respectively. The cholinergic agonist carbachol stimulated GLP-1 secretion in a concentration-dependent manner, maximal release was observed at 1 mM carbachol (228% of the control value). Binding of the muscarinic antagonist [N-methyl-]scopolamine ([3H]NMS) on cell homogenates was time dependent, specific, and saturable. Scatchard analysis revealed one class of receptors (Kd, 14 pM; binding capacity, 20 fmol/mg protein). Carbachol (0.1 microM to 1 mM) dose dependently displaced [3H] NMS binding and increased the intracellular calcium concentration without modification of adenylate cyclase activity. The order of potency of different antagonists, showing a preferential affinity for M1, M2, and M3 muscarinic receptor subtypes, to inhibit [3H]NMS binding, the carbachol-induced increase in intracellular calcium, and carbachol-stimulated GLP-1 secretion, was as follows: atropine (nonselective) > 4-diphenylacetoxy-N-methylpiperidine methiodide (M3) > pirenzepine (M1) > AF-DX 116 (M2). The results of the present study, therefore, demonstrate that secretion of GLP-1 induced by cholinergic agonist depends on muscarinic M3-subtype receptors in the endocrine intestinal cell line STC-1. This system may prove useful to study the cellular mechanisms of GLP-1 secretion.

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Muscarinic Regulation of Somatostatin Release from Primary Cultures of Human Antral Epithelial Cells

Cited by 18 publications

References 16 publications

Regulation of amylin release from cultured rabbit gastric fundic mucosal cells

Regulation of amylin release from cultured rabbit gastric fundic mucosal cells

Transcriptional and Functional Characterization of the G Protein-Coupled Receptor Repertoire of Gastric Somatostatin Cells

Stimulation of glucagon-like peptide-1 secretion by muscarinic agonist in a murine intestinal endocrine cell line.

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