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Blocking dopamine receptor 2 decreases gastrin levels in H. pylori-infected mice through increasing gastric somatostatin content

Published on Monday, 24 August 2026

Abstract

Long-term infection with Helicobacter pylori (H. pylori) leads to elevated serum gastrin levels, which are closely related to gastric cancer. It is important to reduce serum gastrin levels after H. pylori infection.

Dopamine (DA) receptor 1 (D1R) is expressed on G cells in the gastric antrum. Parietal cells produce DA, which inhibits somatostatin (SOM) release through D2R on D cells in the gastric mucosa.

Whether targeted intervention in DRs can improve high gastrin levels after H. pylori infection remains to be explored. In this study, human gastric tissue, H. pylori-infected mice, D1R and D2R knockout mice, RT-qPCR, enzyme-linked immunosorbent assay (ELISA), immunohistochemical (IHC), Western blot, and ex vivo incubation of gastric mucosae were used.

We found that H. pylori infection destroyed the mitochondria of parietal cells and reduced DA content in the gastric mucosa at 10 wk after infection.

Moreover, gastrin-positive cell numbers and serum gastrin levels were increased. D1R, but not D2R, was observed in G cells. DA promoted gastric gastrin secretion. Interestingly, both D1- and D2-like agonists mimicked the effect of DA on the gastrin secretion, which was antagonized by their antagonists.

Blocking D2R with domperidone or knocking out D2R resulted in decreased gastrin-positive cell numbers and gastrin levels but increased SOM levels at 10 wk after H. pylori infection.

Our findings highlight the key regulatory effect of D2R on gastrin secretion and elucidate the role of domperidone in reducing the elevated gastrin level associated with H. pylori infection.

NEW & NOTEWORTHY: We report novel findings that blocking D2Rs, not D1Rs, decreased the number of gastric gastrin-positive cells and gastrin levels in H. pylori-infected mice.

Gastric gastrin secretion induced by DA was indirectly mediated via D2Rs, which suppressed SOM release.

These results provide an experimental basis for local regulation of gastric gastrin secretion by DA through D2Rs, offering a potential strategy for preventing and treating high gastrin levels in H. pylori infection.

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About this publication.

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives since 1977);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

The Di Bella's Method: Use of Prolactin Inhibitors Cabergoline and/or Bromocriptine, Somatostatin/Octreotide analogues and/or derivatives since 1977 associated with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea - together with others chemical compounds: the dosage and administration schedule must be individualised for each patient - in several Oncological Pathologies:

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;