ECL CELLS - BIOLOGY AND PATHOBIOLOGY

During recent years, the so-called ECL cells of the acid-producing part of the stomach have attracted much attention, mainly due to the fact that mice and rats were found to develop gastric carcinoids (ECL cell tumors) following lifelong treatment with blockers of acid secretion. These observations touched off concern about the safety of the long-term clinical use of such drugs. The ECL cells are the predominant endocrine cell population in the oxyntic mucosa. They produce histamine, chromogranin A/pancreastatin and an as yet unidentified peptide hormone. They respond to gastrin by the release of secretory products; more long-term responses include adaptation to the gastrin stimulus, hypertrophy and hyperplasia. Intravenous infusion of maximally effective doses of gastrin promptly reduced the number of cytoplasmic vesicles in the ECL cells and their content of histamine and pancreastatin. Despite the ongoing infusion of gastrin, the number of vesicles and the content of histamine and pancreastatin were back to normal 4-6 h after the start of the infusion. The histidine decarboxylase (HDC) activity and HDC mRNA level increased progressively until plateaus were reached after 6-8 h of gastrin infusion. The size of the ECL cells started to increase about 4 days after the start of a subcutaneous gastrin infusion (resulting in half-maximally effective serum gastrin concentrations). The ECL cell size reached maximum after about 2 weeks and then remained at this level. The number of cytoplasmic vesicles was increased; this effect seemed to reach a maximum after 1-2 weeks. The gastrin-evoked increase in the ECL cell self-replication rate was maximal after 1-2 weeks, after which time there was a gradual return to prestimulation values. The ECL cell density increased fairly slowly and did not reach maximum (more than 4-fold increase) until after 20 weeks of hypergastrinemia (omeprazole treatment). The HDC activity which was elevated by gastrin remained elevated for as long as the gastrin stimulus was maintained (the longest time studied was 20 weeks). The physiological significance of the ECL cells is obscure but probably related to their capacity to produce and store histamine and an as yet unidentified peptide hormone.