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Lin Xiao, Suzana Kovac, Mike Chang, Arthur Shulkes, Graham S Baldwin and Oneel Patel

Introduction The peptide hormone gastrin is secreted by G cells in the gastric antrum and regulates gastric acid secretion in the stomach. Gastrin is synthesized as a large preprohormone of 101 amino acids, which yields progastrin (80 amino acids

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Peng Xu, John J Gildea, Chi Zhang, Prasad Konkalmatt, Santiago Cuevas, Dora Bigler Wang, Hanh T Tran, Pedro A Jose and Robin A Felder

, and the presence of a gastrorenal axis is disputed ( Preston et al. 2012 ). We have reported that a gastrorenal pathway exists in which gastrin secreted into the blood from the stomach, in response to ingested sodium, stimulates the gastrin receptor

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E Grossini, C Molinari, L Sigaudo, M Biella, D A S G Mary and G Vacca

Introduction The gastrointestinal peptide hormone gastrin-17 has been recently found in anaesthetized pigs to cause vasodilation through mechanisms related to nitric oxide (NO) effects ( Grossini et al . 2011 ). NO measurement and protein analysis

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Ian L P Beales and Olorunseun O Ogunwobi

Introduction Glycine-extended gastrin (G-Gly) is a product of processing of the preprogastrin peptide product of the gastrin gene. It is becoming apparent that the different peptide products of this processing have different profiles of biological

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G Monges, P Biagini, J-F Cantaloube, C Chicheportiche, V Frances, D Brandini, P Parc, J-F Seitz, M Giovannini, R Sauvan and J Hassoun

ABSTRACT

To investigate the hypothesis that gastrin might be synthesized by tumour tissues in cancer of the colon, samples from six human colon tumours, one hepatic metastasis, four normal colonic mucosal samples and two antral and one fundic gastric mucosal samples from nine patients were analysed to determine whether gastrin mRNA was present.

RNA was extracted from surgical specimens by ultracentrifugation on a CsC1 cushion, purified using the guanidinium thiocyanate method, reversetranscribed and amplified by polymerase chain reaction. Gastrin mRNA was detected in each colonic carcinoma sample (including the hepatic metastasis), while no such signal was observed in normal colon biopsies. Positive and negative controls (gastric antrum and fundus respectively) gave the expected results. In each of the positive samples, the chemiluminescent revelation of amplified products after Southern blotting corresponded to gastrin mRNA without the intron.

These findings demonstrate the ability of primary and metastatic human colonic tumours to produce gastrin mRNA. Since malignant cell lines have been reported to produce gastrin peptide, and since gastrin receptors were present in some cases, our results support the idea that gastrin may be involved in an autocrine mechanism.

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HL Waldum, IM Kvetnoi, R Sylte, B Schulze, TC Martinsen and AK Sandvik

The peroxisome proliferator ciprofibrate induces hypergastrinemia without inhibiting acid secretion. The present study was carried out to assess the effect of ciprofibrate on serum gastrin and gastrin (G) cells in different strains of rats and to compare the effect of ciprofibrate with other lipid-reducing agents (lovastatin and simvastatin) which have a different mechanism of action. Serum gastrin was determined by a radioimmunoassay method, G cell density by histomorphometry after immunostaining for G cells, and gastrin, somatostatin and histidine decarboxylase (HDC) mRNA abundance by Northern blot analysis. Ciprofibrate (100 mg/kg/day for three weeks) induced a marked hypergastrinemia (P < 0.01) in male and female Fischer rats as well as in female Wistar rats. Simvastatin and lovastatin did not affect serum gastrin. Antral G cell density increased significantly in female Wistar rats (P < 0.05) and non-significantly in the other rats after ciprofibrate. Both gastrin and somatostatin mRNA abundance in antral mucosa increased markedly and significantly (P < 0.01) after ciprofibrate treatment. The present study shows that the peroxisome proliferator ciprofibrate induces hypergastrinemia secondary to an increased storage and synthesis of antral gastrin. Since somatostatin mRNA abundance also increased, the present study suggests that ciprofibrate and possibly other peroxisome proliferators in sufficient concentrations have a stimulatory effect on endocrine cells.

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A G Aprikian, K Han, S Chevalier, M Bazinet and J Viallet

ABSTRACT

Bombesin and gastrin-releasing peptide (GRP) are potent neuropeptides expressed by prostate cancer neuroendocrine cells and are related to the progression of this malignancy. This study characterizes bombesin receptors in human prostate cancer cell lines (PC-3, DU-145, LNCaP) and assesses the in vitro effect of bombesin on signal transduction and cell proliferation. [125I]Tyr4-bombesin binding assays (37 °C) and Scatchard analyses revealed the presence of a single class of high-affinity receptors with similar K d values (1·5, 1·1 and 3·6 × 10−10 m in PC-3, DU-145 and LNCaP cells respectively) but with significant differences in the number of binding sites per cell (47·6, 1·5 and 0·1 × 103 in PC-3, DU-145 and LNCaP cells respectively). Molecular characterization of the binding sites performed in PC-3 cells by cross-linking experiments and SDS/PAGE revealed a single radioactive band of 85 kDa. To determine which of the three known bombesin receptor subtypes (GRP receptor (GRP-R), neuromedin B receptor, bombesin receptor subtype-3) were expressed in the cell lines, reverse transcription/PCR analysis of cellular RNA followed by hybridization with receptor-specific cDNA was performed. This revealed the presence of GRP-R transcript in all cell lines, while neither of the other two receptor transcripts were expressed. When intracellular calcium mobilization was measured by Fura-2/AM cell labeling and spectrofluorometric monitoring, bombesin (100 nm) induced rapid calcium mobilization in both PC-3 (>200% of baseline) and DU-145 (>100% of baseline) cells, but not in LNCaP cells. However, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and [3H]thymidine incorporation, no growth modulation was observed with bombesin or bombesin receptor antagonist at various concentrations (0-500 nm). Our data indicate that bombesin is a potent inducer of signal transduction via GRP-R receptors in androgen-insensitive PC-3 and DU-145 prostate cancer cells. This suggests that the bombesin/GRP family of neuropeptides may play a regulatory role in the biology of androgen-independent prostate cancer.

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I Bakke, AK Sandvik and HL Waldum

The peroxisome proliferator ciprofibrate induces hypergastrinemia and as a consequence, enterochromaffin-like (ECL) cell hyperplasia. The mechanism for the gastrin cell stimulation is unknown. The somatostatin analog octreotide LAR (long-acting release) was used to see if the stimulating effects of ciprofibrate could be attenuated. Female Fischer rats were dosed with ciprofibrate (50 mg/kg body weight per day) alone or combined with octreotide LAR (10 mg/30 days) for 60 days. Plasma gastrin and histamine, gastric endocrine cell densities and mRNA abundances were measured. Ciprofibrate increased gastrin mRNA abundance (P<0.05), gastrin cell number (P<0. 001) and cell area (P<0.01), and induced hypergastrinemia (P<0.001). These rats had profound ECL cell hyperplasia, confirmed by an increase in chromogranin A (CgA) and histidine decarboxylase (HDC) mRNA, density of neuroendocrine and ECL cells and plasma histamine levels (all P<0.001). Octreotide LAR did not affect ciprofibrate stimulation of gastrin cells, but all parameters of ECL cell hyperplasia were reduced (P<0.001). Octreotide LAR also significantly inhibited basal ECL cell function and growth. Ciprofibrate stimulates gastrin cell activity by a mechanism unaffected by octreotide, but octreotide does inhibit basal and gastrin-stimulated ECL cell function and growth.

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Chunheng Mo, Long Huang, Lin Cui, Can Lv, Dongliang Lin, Liang Song, Guoqiang Zhu, Juan Li and Yajun Wang

tract smooth muscle ( Erspamer et al . 1972 ). Subsequently, two structurally and functionally related bombesin-like peptides encoded by separate genes, gastrin-releasing peptide (GRP) and neuromedin B (NMB), have also been identified in mammals

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K J Oliveira, T M Ortiga-Carvalho, A Cabanelas, M A L C Veiga, K Aoki, H Ohki-Hamazaki, K Wada, E Wada and C C Pazos-Moura

bombesin-like peptides and their related receptors, pituitaries from NBR-KO and WT mice were immediately frozen in liquid nitrogen until processed to evaluate mRNA levels of NB, gastrin-releasing peptide (GRP), GRP-receptor (GRP-R) and bombesin receptor