Neurohormonal modulation of rat enterochromaffin-like cell histamine secretion

Sándor, András; Kidd, Mark; Lawton, Gary P.; Miu, Kun; Tang, Laura H.; Modlin, Irvin M.

doi:10.1053/gast.1996.v110.pm8612997

Cited by 55 publications

(49 citation statements)

References 8 publications

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“…Excess gastric acid secretion is an important risk factor that promotes the development of gastric ulcers (24,25), and reducing gastric juice secretion is a useful strategy to prevent and treat gastric ulcers (5). Gastric juice secretion is regulated by the central nervous system (CNS), in particular the vagus nerve system (26). Neuropeptides are able to influence CNS activity and maintain gastric mucosal homeostasis (3).…”

Section: Discussionmentioning

confidence: 99%

Insect tea attenuates hydrochloric acid and ethanol‑induced mice acute gastric injury

Cheng

Qian

et al. 2017

Exp Ther Med

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Abstract. The aim of the present study was to investigate the protective effect of insect tea on HCl/ethanol-induced gastric ulcers in ICR mice. The serum levels of vasoactive intestinal peptide, substance P, somatostatin, motilin and endothelin-1 in mice were assessed using commercial kits and gastric tissues of superoxide dismutase (SOD, nitric oxide (NO) and malondialdehyde (MDA) were determined using western blot analysis Insect tea significantly reduced HCl/ethanol-induced gastric juice secretion and increased the pH of gastric juice (P<0.05). Insect tea treatment signfiicantly increased vasoactive intestinal peptide and somatostatin, and significantly decreased motilin, substance P and endothelin levels in the serum (P<0.05). Treatment with insect tea was demonstrated to significantly increase levels of gastric SOD and NO and to reduce levels of MDA in the gastric ulcer mouse model (P<0.05). The gastric expression of inhibitor of nuclear factor-κB (NF-κB), epidermal growth factor (EGF), EGF receptor, neuronal nitric oxide synthase (nNOS), endothelial NOS, Mn-SOD, Cu/Zn-SOD and catalase was significantly increased in mice treated with inset tea compared with untreated model mice (P<0.05). Levels of NF-κB, and inducible NOS were demonstrated to be decreased in mice treated with insect tea compared with untreated model mice (P<0.05). The results of the present study suggest that insect tea has a protective effect against HCl/ethanol-induced gastric ulcers in ICR mice. This effect may be achieved via modulating serum neuropeptide levels, reducing gastric juice secretion, and modulating the inflammation-and antioxidant-associated protein expressions in gastric tissue.

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Section: Discussionmentioning

confidence: 99%

Insect tea attenuates hydrochloric acid and ethanol‑induced mice acute gastric injury

Cheng

Qian

et al. 2017

Exp Ther Med

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“…In addition, the presence of RNA encoding somatostatin receptor (SSTR) transcripts, adrenergic, dopaminergic, cholinergic, and muscarinic receptor transcripts was assessed, since we and other researchers (Modlin et al 1994, Sandor et al 1996, Lindstrom et al 1997) have demonstrated the relationship of these receptors in the proliferative and secretory regulation of the enterochromaffin-like cells (ECL), the gastric neuroendocrine equivalent of the small intestinal EC cell. The presence of transcripts for putative regulatory receptors in KRJ-I cells was confirmed using reverse transcription (RT)-PCR as described previously.…”

Section: Krj-i Transcriptomementioning

confidence: 99%

Further delineation of the continuous human neoplastic enterochromaffin cell line, KRJ-I, and the inhibitory effects of lanreotide and rapamycin

Kidd

Eick²,

Modlin³

et al. 2007

Journal of Molecular Endocrinology

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Small intestinal carcinoids (SICs) are the most prevalent gastrointestinal carcinoid and characterized by local invasion metastasis and protean symptomatology. The proliferative and secretory regulation of the cell of origin, the enterochromaffin (EC) cell has not been characterized. The absence of either a pure preparation of normal EC cells or human EC carcinoid cell lines has hindered the development of therapeutic agents. We therefore further characterized the neoplastic SIC cell line, KRJ-I by assessing its secretory (serotonin (5-HT)) and proliferative responses and defining its log growth phase transcriptome. Electron microscopy demonstrated oval, lobulated nuclei and substance P, and 5-HT-positive cytoplasmic vesicles. RT-PCR detected transcripts for chromogranin A (CHGA), VMAT1 (SLC18A1), tryptophan hydroxylase (TPH1), substance P (TAC1), guanylin (GUCA2A), and SERT (SLC6A4). By immunohistochemistry, all cells were positive for CHGA, SERT, VMAT1, and TPH1. Transcriptome analysis (Affymetrix U133 Plus chips) identified somatostatin SSTR2/3, adrenergic a1C and b1, dopamine D2, nicotinic-type cholinergic A5, A6, B1, muscarinic acetylcholine M4, and 5-HT-2A receptors. The presence of transcripts for SSTR1, SSTR2, and SSTR3 receptors was confirmed by RT-PCR and sequencing. Isoproterenol (ISO) resulted in a dose-dependent increase in intracellular cAMP (EC 50 Z340 nM) and 5-HT (EC 50 Z81 nM) which was completely inhibited by the cAMP antagonist 2 0 ,5 0 -dideoxyadenosine (10 mM). Preincubation with a SSTR agonist, lanreotide, inhibited Ip-stimulated 5-HT secretion (IC 50 Z420 nM). Both lanreotide (10 nM) and rapamycin (50 nM) inhibited proliferation (20G12 and 35G5% respectively) in serum-free medium whereas gefitinib (1 nM-10 mM) inhibited proliferation at micromolar concentrations. KRJ-I is a neoplastic EC cell line that can be used as an in vitro model of SICs as it will allow elucidation and clarification of the secretory and proliferative mechanism(s) of neoplastic EC cells and the molecular signatures that characterize each of these responses.

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“…The rodent Mastomys develops gastric carcinoids both spontaneously (12-18 mo) and very rapidly (8 -12 wk) when acid suppression and hypergastrinemia are engendered (26,34). In the stomach, the enterochromaffin-like (ECL) cell, which regulates acid secretion under the effect of both gastrin and PACAP (31,40), transforms into a neoplastic phenotype when exposed to hypergastrinemia (34). Gastrin itself has no proliferative effect on ECL cells once neoplastic transformation has occurred and the ECL cells become gastrin autonomous (34).…”

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confidence: 99%

Role of CCN2/CTGF in the proliferation of Mastomys enterochromaffin-like cells and gastric carcinoid development

Kidd¹,

Modlin²,

Eick³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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cell proliferation is initially gastrin driven, but once neoplasia develops, cells become gastrin autonomous. We hypothesized that CCN2 (CTGF), a mitogenic growth factor, may regulate ECL cell proliferation. A Mastomys GeneChip database was examined (dCHIP) to identify CCN2 expression levels. CCN2 in normal and tumor ECL cell preparations obtained using FACS (100 nM acridine orange) was examined by real-time PCR. CCN2 protein was identified in mucosal and ECL cell preparations by immunohistochemistry. Short-term cultured cells were stimulated with either CCN2 or CCN2 ϩ EGF, and proliferation was measured (MTT assay). The ERK1/2 inhibitor PD-98059 (0.1-100 M) was assessed in terms of CCN2 (1 ng/ml)-mediated proliferation and ERK1/2 phosphorylation. CCN2 transcript and protein was then examined in clinical gastric carcinoids. The ccn2 transcript was upregulated in tumor samples compared with the normal mucosa (ϩ2.36-fold, P Ͻ 0.01). PCR demonstrated that ccn2 was not expressed in FACS-prepared (Ͼ98% pure) normal ECL cells but was elevated in tumor ECL cell fractions (41.3 Ϯ 10.7-fold). Immunostaining of the Mastomys gastric mucosa and FACS preparations confirmed that CCN2 protein was present in ECL tumors but not in normal ECL cells. Neither CCN2 nor CCN2 ϩ EGF stimulated normal ECL cell proliferation. CCN2 stimulated tumor proliferation (EC 50 ϳ0.01 ng/ml); EGF significantly augmented (P Ͻ 0.01) CCN2-induced tumor cell proliferation (EC50 ϭ 20 pg/ml). PD-98059 inhibited CCN2-induced proliferation (Ϫ12 Ϯ 3%, P Ͻ 0.05) and ERK1/2 phosphorylation (Ϫ34 Ϯ 5%, P Ͻ 0.05) in tumor cells. In clinical samples, both CCN2 transcript and protein were elevated in gastrin-autonomous carcinoids (P Ͻ 0.02) compared with the normal mucosa. In conclusion, CCN2 may be a proliferative regulator of Mastomys ECL neoplastic proliferation once these cells become autonomous of gastrin regulation. Identification of CCN2 in gastric carcinoid tissue may be useful both as an indicator of ECL cell transformation and may define gastrin autonomy, a criteria of gastric carcinoid malignancy.connective tissue growth factor; epithelial growth factor AGENTS involved in regulating cell proliferation during the development of carcinoids and neuroendocrine (NE) tumors remain an elusive issue. Little information in this area is available since few models and NE cell lines exist to evaluate the problem. The rodent Mastomys develops gastric carcinoids both spontaneously (12-18 mo) and very rapidly (8 -12 wk) when acid suppression and hypergastrinemia are engendered (26, 34). In the stomach, the enterochromaffin-like (ECL) cell, which regulates acid secretion under the effect of both gastrin and PACAP (31, 40), transforms into a neoplastic phenotype when exposed to hypergastrinemia (34). Gastrin itself has no proliferative effect on ECL cells once neoplastic transformation has occurred and the ECL cells become gastrin autonomous (34). Nevertheless, proliferation continues even if the gastrin stimulus is withdrawn, indicating that an alternative proliferativ...

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Neurohormonal modulation of rat enterochromaffin-like cell histamine secretion

Cited by 55 publications

References 8 publications

Insect tea attenuates hydrochloric acid and ethanol‑induced mice acute gastric injury

Insect tea attenuates hydrochloric acid and ethanol‑induced mice acute gastric injury

Further delineation of the continuous human neoplastic enterochromaffin cell line, KRJ-I, and the inhibitory effects of lanreotide and rapamycin

Role of CCN2/CTGF in the proliferation of Mastomys enterochromaffin-like cells and gastric carcinoid development

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