Publications (5)26.53 Total impact

  • No preview · Article · May 2004 · Zeitschrift für Gastroenterologie
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    ABSTRACT: The histidine decarboxylase enzyme (HDC) is responsible for the synthesis of histamine in mammals. Histidine decarboxylase-deficient (HDC-/-) mice have recently been developed by targeted mutation of the HDC gene. The impact of prolonged histamine deficiency was studied on gastric morphology (by immunohistochemistry and morphometry), gastric acid secretion (by a wash-through method for basal gastric acid secretion and by pylorus ligation for stimulated gastric acid secretion) and gastrin levels (by radioimmunoassay) in homozygous HDC-/- mice kept on a low-histamine diet. A double maximal gastric acid secretory response was found in knockouts after exogenous histamine administration. In contrast, the gastric acid secretion was significantly reduced after gastrinergic and cholinergic stimulation in the absence of histamine. The oxynthic gland area of HDC-/- mice was thickened with an increased parietal cell count compared to wild types. Substantially elevated serum and antral tissue gastrin levels of HDC-/- mice could be possible indications of both an expanded parietal cell mass and/or an increased histamine-induced maximal gastric acid secretory capacity of this genotype. These data suggest that not enough compensatory mechanisms develop in HDC-/- mice during a prolonged low-histamine diet to maintain/restore normal gastric acid secretion. An expanded parietal cell pool was also demonstrated in HDC-/- mice kept on a low-histamine diet, probably caused by a trophic effect of sustained hypergastrinaemia. The HDC-/- strain is a suitable model for studying the effects of achlorhydria and consequent hypergastrinaemia as an approach to human conditions such as atrophic gastritis or long-term antisecretory therapies.
    No preview · Article · Mar 2003 · Scandinavian Journal of Gastroenterology

  • No preview · Article · Apr 2001 · Gastroenterology
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    ABSTRACT: Background. Recently we demonstrated that gastric mucosa of rats can synthesize, store and release dopamine. Out of five different subtypes, mRNA of D5 (=D1b) dopamine receptor is very abundant in the gastric epithelium. D1 receptor selective dopamine agonists have been shown to protect against experimental gastro-duodenal lesions. Aims. To test the hypothesis that protective effects of dopamine involve D5 receptors, mucosal lesions were induced in D5 receptor deficient (KO) and wild-type (WT) mice using cysteamine. Morphology and gastric acid secretion of D5 KO mice were also studied. Methods. Single doses of 600 mg/kg, 300 mg/kg cysteamine or vehicle were administered subcutaneously to fasted animals. After 24 h, number and severity of gastro-duodenal lesions were analyzed. Basal and histamine-induced maximal gastric acid output were measured by a stomach-sac wash-through method. Results. All the KOs in the 600 mg/kg cysteamine group died within 4 h showing symptoms of toxicity while three out of four WTs survived (P<0.05). Mortality after 300 mg/kg cysteamine was significantly higher in KOs versus the WTs: 6/14 versus 2/11, P<0.05. Gastric lesion-index was also significantly higher in KOs (median, middle quartile): four (3–9) versus 0 (0-0), P<0.05. Duodenal lesions did not develop from this single dose of cysteamine in either genotype. Basal and histamine-induced maximal gastric acid output were comparable in the two genotypes. Conclusions. This study demonstrates that loss of D5 receptor causes mucosal vulnerability and increased toxicity of cysteamine in genetically manipulated mice. Thus, D5 receptor subtype is indeed likely to be involved in protective effects of dopamine in the stomach.
    No preview · Article · Jan 2001 · Journal of Physiology-Paris
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    B Hunyady · A Zólyomi · B J Hoffman · E Mezey
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    ABSTRACT: Gastrin and histamine both potently stimulate secretion of acid into the gastric lumen. How these agents interact and how their release is controlled is poorly understood. Therefore, we decided to look for histamine in the antral portion of the rat stomach where the gastrin-producing G cells are located. We used immunocytochemical methods to visualize histamine, histidine decarboxylase (HDC, the enzyme that converts histidine to histamine), and the type 1 vesicular monoamine transporter (VMAT1, the protein responsible for moving histamine into vesicles for storage and release). We were surprised to find that histamine, HDC, and VMAT1 were all present in G cells. Our results suggest that G cells synthesize and secrete gastrin and histamine. Whether histamine acts in concert with gastrin to stimulate acid secretion, or functions as an autocrine inhibitor of gastrin release remains to be seen.
    Full-text · Article · Nov 1998 · Endocrinology