Cellular Basis of Pepsinogen Secretion

Hersey, S. J.

doi:10.1002/cphy.cp060314

Cited by 4 publications

(3 citation statements)

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“…With lansoprazole, pepsin output was less suppressed than acid output, as reported by others in early studies of lansoprazole in volunteers 34 . Because lansoprazole acts specifically only on the parietal cell, it is not clear why pepsin secretion was suppressed as much as it was (–67% for BPO and –42% for PPO), as there are no described connections or interactions between parietal and the adjacent peptic cells 35 . The evidence suggests that such connections might well exist.…”

Section: Discussionmentioning

confidence: 99%

Long‐term lansoprazole control of gastric acid and pepsin secretion in ZE and non‐ZE hypersecretors: a prospective 10‐year study

Hirschowitz

Simmons

Mohnen

2001

Aliment Pharmacol Ther

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Background: The majority of patients with Zollinger–Ellison syndrome require lifelong treatment with proton pump inhibitors. Aims: To determine the efficacy of lansoprazole control of acid and pepsin secretion over the long term in Zollinger–Ellison syndrome and non‐Zollinger–Ellison syndrome hypersecretors. Methods: Sixty‐three hypersecretors (basal acid output > 15 mmol/h), 46 Zollinger–Ellison syndrome and 17 non‐Zollinger–Ellison syndrome, with a total history of 15.4 and 19.2 years, respectively, were entered into a long‐term prospective study using lansoprazole. Sixty‐one were studied every 3 months for 1 year and then every 3–6 months up to 10 years during lansoprazole treatment with endoscopy, serum gastrin and gastric analysis, measuring both basal and stimulated pH and acid and pepsin secretion. Doses were individually optimized and adjusted to keep the basal acid output at < 5 mmol/h in intact patients and < 1 mmol/h in antrectomized Zollinger–Ellison syndrome patients. Results: The dose of lansoprazole could not be predicted a priori from pre‐treatment acid or pepsin output, serum gastrin, prior omeprazole dose or diagnosis or prior complications. The median dose was ∼ 80 mg/day, with a wide range from 15 mg every other day to 360 mg/day, and generally stabilized by 12 months. However, as doses were adjusted over time for indications, almost half the patients required higher doses. With adjustments, the basal acid output was maintained in the target range in > 90% of intact patients and in 80% of antrectomized patients. Gastric juice pH increased from ∼ 1.2 before therapy to > 3.4 during therapy. Serum gastrin in Zollinger–Ellison syndrome patients, after excluding five outliers, did not change over the course of therapy, but doubled in non‐Zollinger–Ellison syndrome patients. There were no adverse events due to lansoprazole, and routine laboratory studies remained normal. Conclusions: The dose of lansoprazole for hypersecretors cannot be predicted, and thus needs to be optimized empirically on an individual basis. With continued periodic adjustments, almost half the patients required increased doses, while safe dose reduction was possible in only one‐quarter. When individually optimized, lansoprazole proved to be safe and effective in the control of secretion for the treatment of both Zollinger–Ellison syndrome and non‐Zollinger–Ellison syndrome hypersecretors for up to 10 years.

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Section: Discussionmentioning

confidence: 99%

Long‐term lansoprazole control of gastric acid and pepsin secretion in ZE and non‐ZE hypersecretors: a prospective 10‐year study

Hirschowitz

Simmons

Mohnen

2001

Aliment Pharmacol Ther

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“…Factors controlling PG secretion in the stomach are well documented (Reviewed by [1,9]). In comparison there are relatively few reports determining the mechanisms controlling the regulation of PG gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…Pepsin substrate specificity is broad, but the enzyme is known to 302 preferentially cleave peptide bonds formed by aromatic residues. (For reviews see [1,2]). …”

Section: Introductionmentioning

confidence: 99%

Pepsinogen C Expression in Intestinal IEC-6 Cells

Wells

Brown

Hall

2003

Cell Physiol Biochem

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Pepsinogen C (PGC) is the inactive precursor of pepsin C, which is a member of the aspartic proteinase family of proteolytic enzymes, and is found within the vertebrate stomach. The precursor molecule is synthesised within the gastric epithelial cells and secreted into the gastric lumen where it undergoes an autocatalytic activation under acidic conditions to the proteolytic molecule. However, the synthesis of PGC has also been reported in numerous non-gastric tissues including the prostate gland and the Brunner’s gland of the small intestine. The physiological significance of PGC in these tissues is not known and studies are limited by the lack of appropriate in vitro cell models. We report here the use of the rat intestinal cell line, IEC-6, as an in vitro model to study the role of pepsinogen C in the intestine. PGC expression was detected in the IEC-6 cells by RT-PCR and immunocytochemistry, using a PGC specific antibody, localised the protein to cytoplasmic secretory granules. Enzymatic assay confirmed the presence of a functional protein exhibiting pepsin activity. Using semi-quantitative RT-PCR we showed that PGC gene expression was up-regulated by the gastro-intestinal hormones gastrin and secretin, and forskolin which stimulates adenylate cyclase activity. This study demonstrates that the IEC-6 cells provide a unique in vitro model for studying pepsinogen C and its potential role(s) in the small intestine.

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