Expanded parietal cell pool in transgenic mice unable to synthesize histamine.
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 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.


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 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.
Hunyady
B
B
First Dept. of Medicine, Medical Faculty, University of Pécs, Pécs, Hungary. bhunyady@yahoo.com
Zólyomi
A
A
Czimmer
J
J
Mózsik
G
G
Kozicz
T
T
Buzás
E
E
Tanaka
S
S
Ichikawa
A
A
Nagy
A
A
Palkovits
M
M
Falus
A
A
D000126:Achlorhydria / Q000503:physiopathology; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D004032:Diet; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D006632:Histamine / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology; D006640:Histidine Decarboxylase / Q000235:genetics; D006720:Homozygote; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000378:metabolism* / Q000473:pathology; D010418:Pentagastrin / Q000494:pharmacology
D005755:Gastrins; D018721:Muscarinic Agonists; D018723:Bethanechol; D006632:Histamine; D006640:Histidine Decarboxylase; D010418:Pentagastrin