THE REGULATION OF HISTIDINE-DECARBOXYLASE GENE-EXPRESSION

Histamine is a biogenic amine, which is involved in a variety of biolo gic processes comprising inflammation, allergic responses, neurotransm ission and regulation of gastric acid secretion. The key enzyme for th e generation of histamine is histidine decarboxylase (HDC), which conv erts the amino acid L-histidine to histamine. In this article, we revi ew the history, biochemistry and molecular biology of this enzyme. Nor thern blot studies in rats demonstrated that HDC gene expression in th e stomach and liver are developmentally regulated with highest levels of expression in the late fetal state, indicating a role of the gene i n growth and development. In the stomach of adult rats, HDC mRNA level s are elevated after omeprazole-induced hypergastrinemia, and in situ hybridization showed that expression of HDC is restricted to the gland ular area in which ECL cells are located. Since no permanent ECL cell line is at hand for in vitro studies, we established a suitable cell s ystem by stable transfection of a human gastric adenocarcinoma cell li ne (AGS) with the CCK-B/gastrin receptor. Transfection of this AGS-B c ell line with reporter gene constructs comprising 5'-flanking DNA sequ ence of the HDC gene joined to the firefly luciferase gene revealed tr anscriptional regulation of the HDC promoter by gastrin through a prot ein-kinase C-dependent pathway. Taken together, these studies are cons istent with the concept of HDC transcriptional regulation as at least one phase of the overall response to gastrin.