Altered influence of CCK-B/gastrin receptors on HDC expression in ECL cells after neoplastic transformation

Gastrin is one of the main factors controlling enterochromaffin-like (ECL) cell endocrine function and growth. Long-standing hypergastrinemia may give rise to ECL cell carcinoids in the gastric corpus in man and in experiment al models. We have analysed the expression and function of CCK-B/gastrin re ceptors in normal ECL cells and in ECL cell tumours (gastric carcinoids) of the African rodent Mastomys natalensis. Hypergastrinemia induced by short- term (5 days) histamine(2)-receptor blockade (loxtidine) resulted in increa sed histidine decarboxylase (HDC) mRNA expression in the gastric oxyntic mu cosa. This increase was significantly and dose-dependently reversed by sele ctive CCK-B/gastrin receptor blockade (YM022). Long-term (12 months) hyperg astrinemia, induced by histamine(2)-receptor blockade, gave rise to ECL cel l carcinoids in the gastric oxyntic mucosa. CCK-B/gastrin receptor mRNA was only slightly elevated while HDC mRNA expression was eight-fold elevated i n ECL cell carcinoids and was not influenced by CCK-B/gastrin receptor bloc kade. Thus CCK-B/gastrin receptor blockade of hypergastrinemic animals redu ces the HDC mRNA expression in normal mucosa but not in ECL cell carcinoids . These results demonstrate that HDC mRNA expression in neoplastic ECL cell s is not controlled by CCK-B/gastrin receptors. (C) 1999 Elsevier Science B .V. All rights reserved.