HISTIDINE-DECARBOXYLASE EXPRESSION AND HISTAMINE-METABOLISM IN GASTRIC OXYNTIC MUCOSA DURING HYPERGASTRINEMIA AND CARCINOID-TUMOR FORMATION

Histamine is an important stimulator of gastric acid secretion. In exp erimental animals, inhibition of acid secretion by long term histamine , receptor blockade causes hypergastrinemia, proliferation of enteroch romaffin-like (ECL) cells, and formation of histamine-producing gastri c 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. Administrat ion of exogenous gastrin to normal animals increased histidine decarbo xylase (HDC) messenger RNA (mRNA) expression in the oxyntic mucosa wit hin 30 min, indicating that gastrin stimulates histamine synthesis by regulating HDC mRNA abundance. Endogenous hypergastrinemia, induced by short term histamine, receptor blockade (loxtidine) for 3-29 days, di d 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. Lung term histamine, 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 con tents of the oxyntic mucosa. Urinary excretion of the histamine metabo lite methyl-imidazole-acetic acid was 2-fold elevated. Tumor-bearing a nimals recovering from histamine, receptor blockade were normogastrine mic and had normal levels of HDC mRNA and histamine in the oxyntic muc osa as well as normal excretion of methyl-imidazole-acetic acid. The r esults indicate that ECL cell carcinoids developing during hypergastri nemia are well differentiated tumors that respond to high gastrin leve ls with increased histamine synthesis and secretion.