Histamine metabolism of gastric carcinoids in Mastomys natalensis

Pharmacological inhibition of gastric acid secretion and subsequent hyperga strinemia in Mastomys natalensis is an experimental model well suited for t he study of gastric carcinoid formation. The genetic susceptibility of Mast omys to develop such tumors is a feature reminiscent of the situation in pa tients with the MEN-1 Zollinger Ellison syndrome, in whom tumor-induced hyp ergastrinemia promotes the development of gastric carcinoids. Chronic hyper gastrinemia, induced by the irreversible H-2-receptor antagonist loxtidine will cause carcinoid formation in Mastomys already after four to six months . As in humans, gastric carcinoids in Mastomys are mainly composed of enter ochromaffinlike (ECL) cells and have low malignant potential. Administratio n of exogenous gastrin to normal young animals increases the expression of histidine decarboxylase (HDC) mRNA in the oxyntic mucosa within 30 minutes. Endogenous hypergastrinemia, induced by short-time loxtidine treatment (th ree to 29 days) enhances the expression of HDC mRNA, histamine contents and ECL cell numbers in the oxyntic mucosa. Long-term loxtidine treatment (sev en to 21 months) results in sustained hypergastrinemia and tumor formation. Tumor-bearing animals exhibited an increase in HDC mRNA and histamine cont ent in the oxyntic mucosa as well as increased urinary excretion of the mai n histamine metabolite, tele-methylimidazole acetic acid (MeImAA). Subseque nt to cessation of loxtidine treatment for two weeks, all parameters of his tamine metabolism were normalized in tumor-bearing animals. These results i ndicate that gastric carcinoids developing during hypergastrinemia are well -differentiated neoplasms whose histamine synthesis and metabolism is regul ated by plasma gastrin.