CHRONIC USE OF PROTON PUMP INHIBITORS AND THE QUANTITY OF G, D, AND ECL CELLS IN THE STOMACH

ABSTRACT Background: Acid inhibition from chronic proton pump inhibitor use and a possible increase in gastrin can lead to changes in the regulation of hydrochloric acid production. However, it has not known whether such chronic use changes the presence of gastrin, delta, and enterochromaffin-like cells in the stomach or the relationship between gastrin and delta cells. Aim: To analyze the number of gastrin-producing gastrin cells, somatostatin-producing cells, and histamine-producing cells in patients who were chronic users of proton pump inhibitor, with or without related Helicobacter pylori infection. Methods: Biopsies from 105 patients, including 81 chronic proton pump inhibitor users (experimental group) and 24 controls, were processed immunohistochemically and subjected to counting of gastrin, delta, and enterochromaffin-like cells in high-magnification microscopic fields and in 10 glands. Results: Gastrin cell, delta cell, and enterochromaffin-like cells counts were similar across the groups and appeared to be unaffected by Helicobacter pylori infection. The ratio between gastrin cells and delta cells was higher in the chronic users of proton pump inhibitor group than in controls. Conclusion: Chronic users of proton pump inhibitor does not affect gastrin cell, delta cell, and enterochromaffin-like cell counts significantly, but may alter the ratio between gastrin cells and delta cells.

PERAN SEL GASTRIN (SEL G) DALAM SALURAN PENCERNAAN

Gastrin cell is one of the enteroendocrine cells in piloric antrum that secretes gastrin. Gastrin is secreted when there are stimuli of food (protein, caffeine, red chili, and alcohol) and vagal nerve. Gastrin is released by exocytosis into the blood and transported to parietal cells. Moreover, this gastrin interacts with CCK2 receptors in enterochromaffin-like cells, and releases histamin that interacts with parietal cells to induce hydrochloric acid production. Besides that, gastrin stimulates secretion of pancreatic enzymes, liver bile flow, and resting tonus of lower esophagal sphincter, but inhibit gastric emptying. Lack of gastrin can cause hypochlorhydria. Gasrin over production can occur in inflammatory states such as gastritis and peptic ulcer, and pancreatic tumor (Zollinger-Ellison syndrome). Key words: gasrin, gastrin cell, hydrochloric acid, parietal cell. Abstrak: Sel gastrin merupakan salah satu sel enteroendokrin yang terletak dalam antrum pilorus dan berfungsi menyekresi hormon gastrin. Gastrin disekresi saat terjadi rangsangan seperti makanan (protein, kafein, cabe merah dan alkohol) serta rangsangan vagus. Gastrin dilepaskan secara eksositosis ke dalam darah dan diangkut ke sel parietal. Gastrin berinteraksi dengan reseptor CCK2 (CCK2R) pada sel enterochromaffin-like (ECL), dan membebaskan histamin yang kemudian berinteraksi dengan sel parietal untuk menginduksi sekresi asam lambung. Selain itu gastrin merangsang sekresi enzim pankreas, aliran empedu hati, tonus istirahat sfingter esofagus bagian bawah, tetapi menghambat pengosongan lambung. Kekurangan gastrin dapat menyebabkan terjadinya hipoklorhidria. Kelebihan gastrin dapat terjadi beberapa keadaan inflamasi lambung seperti gastritis dan ulkus peptikum serta adanya tumor pankreas gastrinoma (sindrom Zollinger-Ellison). Kata kunci: gastrin, sel gastrin, asam lambung, sel parietal.

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

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.

Parenterally or enterally administered anti-somatostatin antibody induces increased gastrin in suckling rats

This study demonstrates the effectiveness of parenteral and oral anti-somatostatin monoclonal antibody to stimulate gastrin cell activity in suckling rats. Intraperitoneal anti-somatostatin monoclonal antibody increased serum gastrin concentration (> 2-fold), and orally administered antibodies retained their neutralizing capabilities as demonstrated by a 30% induction of gastrin synthesis. Absorption of luminal monoclonal antibody was time dependent and saturable as demonstrated by measurement of serum murine immunoglobulin G and the subsequent effects on serum gastrin and antral gastrin mRNA concentrations. Enhanced gastrin synthesis after oral administration required whole antibody in that enterally delivered F(ab')2 fragments were not absorbed and did not increase serum gastrin concentrations. In addition, pretreatment with excess Fc fragments decreased monoclonal antibody absorption and eliminated the serum gastrin response to oral monoclonal antibody. These results demonstrate that orally administered murine anti-somatostatin monoclonal antibody was rapidly and efficiently absorbed via an Fc-dependent mechanism and retained immunoneutralizing activity against endogenous somatostatin, neutralizing its inhibition of gastrin cell activity. These results indicate that orally administered monoclonal antibodies could potentially be used to determine the role of other peptides and growth factors as potential physiological regulators during the suckling period of postnatal development.