Octreotide inhibits the enterochromaffin-like cell but not peroxisome proliferator-induced hypergastrinemia

Bakke, Ingrid; Sandvik, A. K.

doi:10.1677/jme.0.0250109

Cited by 19 publications

(15 citation statements)

References 39 publications

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“…Normally, there is a reciprocal relationship between the activity of the antral G and D cells (6,76). During ciprofibrate dosing, we found a concomitant increase in gastrin and somatostatin mRNA abundance in the antral mucosa (3,70). To our knowledge, this had not been reported previously.…”

supporting

confidence: 46%

Ciprofibrate stimulates the gastrin-producing cell by acting luminally on antral PPAR-α

Martinsen¹,

Bakke²,

Chen³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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dum. Ciprofibrate stimulates the gastrin-producing cell by acting luminally on antral PPAR-␣. Am J Physiol Gastrointest Liver Physiol 289: G1052-G1062, 2005. First published August 11, 2005; doi:10.1152/ajpgi.00268.2005.-The lipid-lowering drug ciprofibrate stimulates gastrin-producing cells in the rat stomach without lowering gastric acidity. Although suggested to be a luminal action on antral peroxisome proliferator-activated receptor-␣ (PPAR-␣), the mechanism is still not fully elucidated. Gastric bypass was surgically prepared in male Sprague-Dawley rats. Gastric-bypassed and shamoperated rats were either given ciprofibrate (50 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 in methocel) or vehicle alone for 7 wk. PPAR-␣ knockout (KO) and wild-type (WT) mice were either given ciprofibrate (500 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 in methocel) or vehicle alone for 2 wk. The concentration of gastrin in blood was analyzed. Antral G cell density and gastrin mRNA abundance were determined by using immunostaining and Northern blot analysis. Ciprofibrate did not raise plasma gastrin or G cell density in gastric-bypassed rats, although the gastrin mRNA level was slightly increased. In contrast, ciprofibrate induced hypergastrinemia, a 50% increase in G cell density, and a threefold increase in gastrin mRNA in sham-operated rats. In PPAR-␣ KO mice, ciprofibrate did not raise G cell density or the gastrin mRNA level. The serum gastrin level was reduced by ciprofibrate. In WT mice, ciprofibrate induced hypergastrinemia, a doubling of G cell density, and a threefold increase in gastrin mRNA. Comparing animals dosed with vehicle only, PPAR-␣ KO mice had higher serum gastrin concentration than WT mice. We conclude that the main effects of ciprofibrate on G cells are mediated from the antrum lumen, and the mechanism is dependent on PPAR-␣. The results indicate that PPAR-␣ may have a role in the physiological regulation of gastrin release.peroxisome proliferator-activated receptor-␣; hypergastrinemia; gastric bypass; peroxisome proliferator-activated receptor-␣ knockout mice IN 1905, EDKINS (19) postulated the presence of a humoral gastric acid secretagogue being released from the antral mucosa. This was confirmed by Gregory et al. (24) in 1966, who identified this secretagogue as gastrin. Gastrin is still the only known gut hormone released from the stomach that mediates gastric acid secretion. The secretagogue effect of gastrin is mediated by the gastrin receptor on the histamine-containing ECL cells (25,56,72). When activated, the ECL cells respond with increased production (55) and release of histamine (56), which stimulates acid secretion from parietal cells by acting on histamine-2 receptors (38,39,71). In addition, gastrin is acknowledged to be the most important growth factor in the oxyntic mucosa (26,73,77). The trophic effect of gastrin is also mediated by the gastrin receptor (77). Consequently, the ECL cell constitutes the main target of gastrin in the regulation of both function and growth of the oxyntic mucosa (7). Long-term hypergastrinemia leads to ...

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supporting

confidence: 46%

Ciprofibrate stimulates the gastrin-producing cell by acting luminally on antral PPAR-α

Martinsen¹,

Bakke²,

Chen³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Finally, we found that gastric endocrine tumor regressed in three patients who had ZES and a family history of multiple type I endocrine neoplasia after long-term treatment with somatostatin analogs (Tomassetti et al 2000). The regression of the tumors was related to the decrease in serum gastrin levels and the hypothetic antiproliferative effect of somatostatin analogs on ECL-cells in both animals and humans , Bakke et al 2000, Tomassetti et al 2000, Erlandsen et al 2007). …”

Section: Discussionmentioning

confidence: 79%

Gastric endocrine tumors type I: treatment with long-acting somatostatin analogs

Campana¹,

Nori²,

Pezzilli³

et al. 2008

Endocrine Related Cancer

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Gastric endocrine tumors associated with autoimmune chronic atrophic gastritis (gastric carcinoid type I) are almost exclusively benign lesions with little risk of deep invasion of the gastric parietal wall. For this reason, the role of octreotide in the treatment of these neoplastic lesions is controversial. Nine patients with more than five type I gastric endocrine tumors each !1 cm in size, without invasion of the muscularis propria and with Ki-67 index lower than 3%, were treated with long-acting somatostatin analogs for 12 months. After 6 months and again after 12 months, all the patients underwent upper gastrointestinal (GI) endoscopy with multiple biopsies. The plasma chromogranin A (CgA) levels and the gastrin levels in the serum were also determined. In all patients, the gastric neoplastic lesions disappeared after 12 months of somatostatin analog therapy. We also observed a significant reduction of CgA and gastrin levels at 6 and at 12 months of therapy as compared with the baseline values. We demonstrate that somatostatin analog treatment provokes the pathological regression of type I gastric carcinoids. This therapeutic approach should be considered as a valid option in selected patients with multiple type I gastric endocrine tumors.

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“…Fischer rats were purchased from Møllegaard Breeding Center (Skensved, Denmark). Dosing of the animals with ciprofibrate was as described previously (5). Briefly, female Fischer rats (200-250 g) were given tap water (control group) or ciprofibrate (50 mg/kg body wt), by gastric intubation, once daily for 60 days.…”

Section: Methodsmentioning

confidence: 99%

Liver gene expression in rats in response to the peroxisome proliferator-activated receptor-α agonist ciprofibrate

Yadetie

Lægreid

Bakke

et al. 2003

Physiological Genomics

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Fibrate class hypolipidemic drugs such as ciprofibrate activate the peroxisome proliferator-activated receptor-α (PPARα), which is involved in processes including lipid metabolism and hepatocyte proliferation in rodents. We examined the effects of ciprofibrate (50 mg/kg body wt per day for 60 days) on liver gene expression in rats using cDNA microarrays. The 60-day dosing period was chosen to elucidate both the metabolic and proliferative actions of this substance, while avoiding confounding effects from the hepatic carcinogenesis seen during more long-term stimulation. Ciprofibrate changed the expression of many genes including previously known PPARα agonist-responsive genes involved in processes such as lipid metabolism and inflammatory responses. In addition, many novel candidate genes involved in sugar metabolism, transcription, signal transduction, cell proliferation, and stress responses appeared to be differentially regulated in ciprofibrate-dosed rats. Ciprofibrate also resulted in significant increases in liver weight and hepatocyte proliferation. The cDNA microarray results were confirmed by Northern blot analysis for selected genes. This study thus identifies many genes that appear to be differentially regulated in ciprofibrate-dosed rats, and some of these are potential targets of PPARα. The functional diversity of these candidate genes suggests that most of them are likely to be differentially regulated as indirect consequence of the many processes affected by ciprofibrate in rodent liver. Although caution is advisable in the interpretation of genome-wide expression data, the genes identified in the present study provide candidates for further studies that may give new insight into the mechanisms of action of peroxisome proliferators.

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Octreotide inhibits the enterochromaffin-like cell but not peroxisome proliferator-induced hypergastrinemia

Cited by 19 publications

References 39 publications

Ciprofibrate stimulates the gastrin-producing cell by acting luminally on antral PPAR-α

Ciprofibrate stimulates the gastrin-producing cell by acting luminally on antral PPAR-α

Gastric endocrine tumors type I: treatment with long-acting somatostatin analogs

Liver gene expression in rats in response to the peroxisome proliferator-activated receptor-α agonist ciprofibrate

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