Histidine decarboxylase expression and histamine metabolism in gastric oxyntic mucosa during hypergastrinemia and carcinoid tumor formation.

Abstract

Histamine is an important stimulator of gastric acid secretion. In experimental animals, inhibition of acid secretion by long term histamine2 receptor blockade causes hypergastrinemia, proliferation of enterochromaffin-like (ECL) cells, and formation of histamine-producing gastric carcinoids. The aim of this study was to examine the role of gastrin in histamine synthesis and metabolism of the oxyntic mucosa of normal, hyperplastic, and carcinoid-bearing Mastomys natalensis. Administration of exogenous gastrin to normal animals increased histidine decarboxylase (HDC) messenger RNA (mRNA) expression in the oxyntic mucosa within 30 min, indicating that gastrin stimulates histamine synthesis by regulating HDC mRNA abundance. Endogenous hypergastrinemia, induced by short term histamine2 receptor blockade (loxtidine) for 3-29 days, did not induce tumors, but enhanced the expression of HDC mRNA (2- to 4-fold elevated) and histamine contents (2-fold elevated) in the oxyntic mucosa. Long term histamine2 receptor blockade (7-21 months) resulted in sustained hypergastrinemia and ECL tumor formation. Tumor-bearing animals had a 4-fold increase in HDC mRNA expression and histamine contents of the oxyntic mucosa. Urinary excretion of the histamine metabolite methyl-imidazole-acetic acid was 2-fold elevated. Tumor-bearing animals recovering from histamine2 receptor blockade were normogastrinemic and had normal levels of HDC mRNA and histamine in the oxyntic mucosa as well as normal excretion of methyl-imidazole-acetic acid. The results indicate that ECL cell carcinoids developing during hypergastrinemia are well differentiated tumors that respond to high gastrin levels with increased histamine synthesis and secretion.

Isolation, functional characterization, and transcriptome of Mastomys ileal enterochromaffin cells

“…Small intestinal mucosa were obtained after the animals were euthanized, washed in PBS, and immersed in 4% formaldehyde overnight (28). Fixed tissue was mounted edge-on in paraffin blocks.…”

“…With the use of elutriation and Nycodenz gradient centrifugation of everted normal and carcinoid-containing stomachs, 85-95% pure preparation of gastric EC-like (ECL) cells can be obtained (26,31). Studies of purified gastric ECL cells have demonstrated the key regulatory role of the histamine enzyme histidine decarboxylase in gastric ECL cell histamine secretion, identified the presence of gastrin CCK 2 and PACAP receptors and defined their key roles in proliferation and secretion (28,31,32,50), and delineated the presence of SST receptor 2 (SST R 2) and the inhibitory role of octreotide in both secretion and proliferation (4,45). With the use of a somewhat similar approach, preparations of neurotensin and enteroglucagon cells have been obtained from the canine ileum (2,6).…”

Intracellular Localization of the 74- and 53-kDa Forms ofl-Histidine Decarboxylase in a Rat Basophilic/Mast Cell Line, RBL-2H3

“…It is the only enzyme that forms histamine in mammals. Histamine is well known to act as an important physiological modulator (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). HDCs have been purified from the soluble fraction of various tissues and found to be a dimer consisting of two identical 53-kDa subunits (13)(14)(15)(16), while the size of cDNA-deduced HDC is around 74 kDa (17)(18)(19).…”

Determination of the histamine metabolite tele-methylimidazoleacetic acid and of creatinine in urine by the same HPLC system

“…The broad range of excretion values (0.9 to 30 mmol/mol creatinine), from normal up to a high level as found here in two patients with systemic mastocytosis, indicate that the method can be satisfactorily applied for evaluation of histamine turnover under various clinical conditions. Moreover, the method has also been successfully used for t-MeImAA analysis in some laboratory animals, as reported for mastomys [22] and rat [23]. The HPLC chromatograms obtained from these animal urines looked very similar to human ones, and interestingly the excretion of t-MeImAA was of the same order of magnitude as in man when corrected for the creatinine excretion.…”