Abstract
Background: 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. Methods: The impact of prolonged histamine deficiency was studied on gastric morphology (by immunohistochemistry and morphometry), gastric acid secretion (by a washthrough 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. Results: 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. Conclusions: 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 atrophic 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.
| Original language | English |
|---|---|
| Pages (from-to) | 133-140 |
| Number of pages | 8 |
| Journal | Scandinavian Journal of Gastroenterology |
| Volume | 38 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2003 |
| Externally published | Yes |
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Keywords
- Gastric acid secretion
- Gastrin
- Histamine
- Histidine decarboxylase enzyme
- Immunohistochemistry
- Transgenic mice
ASJC Scopus subject areas
- Gastroenterology
Cite this
Expanded parietal cell pool in transgenic mice unable to synthesize histamine. / Hunyady, B.; Zólyomi, A.; Czimmer, J.; Mózsik, G.; Kozicz, T.; Buzás, E.; Tanaka, S.; Ichikawa, A.; Nagy, A.; Palkovits, M.; Falus, A.
In: Scandinavian Journal of Gastroenterology, Vol. 38, No. 2, 01.02.2003, p. 133-140.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expanded parietal cell pool in transgenic mice unable to synthesize histamine
AU - Hunyady, B.
AU - Zólyomi, A.
AU - Czimmer, J.
AU - Mózsik, G.
AU - Kozicz, T.
AU - Buzás, E.
AU - Tanaka, S.
AU - Ichikawa, A.
AU - Nagy, A.
AU - Palkovits, M.
AU - Falus, A.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Background: 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. Methods: The impact of prolonged histamine deficiency was studied on gastric morphology (by immunohistochemistry and morphometry), gastric acid secretion (by a washthrough 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. Results: 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. Conclusions: 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 atrophic 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.
AB - Background: 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. Methods: The impact of prolonged histamine deficiency was studied on gastric morphology (by immunohistochemistry and morphometry), gastric acid secretion (by a washthrough 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. Results: 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. Conclusions: 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 atrophic 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.
KW - Gastric acid secretion
KW - Gastrin
KW - Histamine
KW - Histidine decarboxylase enzyme
KW - Immunohistochemistry
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=0037299986&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037299986&partnerID=8YFLogxK
U2 - 10.1080/00365520310000591
DO - 10.1080/00365520310000591
M3 - Article
C2 - 12678328
AN - SCOPUS:0037299986
VL - 38
SP - 133
EP - 140
JO - Scandinavian Journal of Gastroenterology
JF - Scandinavian Journal of Gastroenterology
SN - 0036-5521
IS - 2
ER -