Achlorhydria induced changes in gastrin, somatostatin, H+/K+-ATPase and carbonic anhydrase in the sheep

doi:10.1016/0167-0115(92)90080-E

Regulatory Peptides

Volume 40, Issue 1, 2 July 1992, Pages 13-27

https://doi.org/10.1016/0167-0115(92)90080-E Get rights and content

Abstract

Gastrin, somatostatin, H⁺/K⁺-ATPase and carbonic anhydrase are principal elements of acid secretion. We investigated in the conscious sheep the effect of 24 h omeprazole (an H⁺/K⁺-ATPase inhibitor) infusion on these elements at the level of synthesis, storage and secretion.

Omeprazole inhibited acid secretion - pH increased from 3.0 to 7.1 at 24 h. Plasma amidated and glycine extended gastrin increased 3-fold while the ratio of amidated to glycine extended gastrins (4:1) remained unchanged. Despite the increase in circulating gastrin, antral gastrin concentration and mRNA did not change significantly. Gastrin-17 (amidated and glycine extended) was the predominant form in the circulation and antrum, although there were preferential increases in larger forms following omeprazole treatment.

Omeprazole had no effect on somatostatin mRNA or peptide levels in the fundus. Similarly, plasma somatostatin remained unchanged. However, antral somatostatin increased significantly (63%) following omeprazole treatment accompanied by a 4-fold increase in its mRNA. Fundic H⁺/K⁺-ATPase mRNA was unchanged but a significant increase (87%) in carbonic anhydrase II mRNA was observed.

Omeprazole induced hypergastrinaemia occurred without a measurable reduction in storage or increased synthesis of gastrin at 24 h. Increased antral somatostatin synthesis and storage may result from stimulation by plasma gastrin on antral D cells, independent of acid. The rise in carbonic anhydrase II mRNA in the absence of any change in H⁺/K⁺-ATPase mRNA may reflect the differential sensitivity of the genes encoding these two enzymes to the stimulatory action of gastrin.

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Somatostatin plays a role in the regulation of gastric acid secretion. Omeprazole, a potent inhibitor of gastric acid secretion, has been reported to cause either a significant decrease or increase in the formation of gastric somatostatin-producing cells. Therefore, we determined in the present study distribution patterns of somatostatin mRNA and protein in fundus mucosa of rats after long-term inhibition of gastric acid secretion. Female Sprague-Dawley rats were given 0, 20 and 100 mg/kg/day omeprazole, respectively, as gastric instillations during 2 months. Serum gastrin levels were significantly higher in the third group than in the other groups. The omeprazole-treated groups also showed an increase in the number of somatostatin-containing cells in fundus mucosa. Moreover, the intensity of somatostatin-positivity was higher in the treated groups than in the control group. We also observed an increase in the number of cells containing somatostatin mRNA in fundus mucosa of omeprazole-treated rats. These results suggest that long-term inhibition of acid secretion does not inhibit but stimulate somatostatin production in mucosa of rat gastric fundus.
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Achlorhydria induced changes in gastrin, somatostatin, H+/K+-ATPase and carbonic anhydrase in the sheep

Abstract

Gastroenterology

J. Clin. Invest.

Am. J. Physiol.

J. Biol. Chem.

Biochem. J.

Physiol. Rev.

Biochemistry

J. Endocrinol.

Am. J. Physiol.

Endocrinology

Gut

Gastrointestinal Hormones

Gastrin

N. Eng. J. Med.

Gastrin

N. Eng. J. Med.

The physiology of gastric acid secretion

N. Eng. J. Med.

Role of circulating somatostatin in regulation of gastric acid secretion, gastrin release and islet cell function

J. Clin. Invest.

Gastrin and somatostatin secretion by perfused rat stomach: functional linkage of antral peptides

Am. J. Physiol.

Paracrine regulation of gastric acid secretion by fundic somatostatin

Am. J. Physiol.

Regulation of gastric somatostatin secretion in the mouse by luminal acidity: a local feedback mechanism

Gastroenterology

Inhibition of gastric acid secretion by omeprazole in the dog and rat

Gastroenterology

The secretory kinetics of the G cell in omeprazole-treated rats

Gastroenterology

Gastrin

Peptide α-amidation

Annu. Rev. Physiol.

Achlorhydria induced changes in gastrin, somatostatin, H⁺/K⁺-ATPase and carbonic anhydrase in the sheep