ECL CELLS OF THE RAT STOMACH - DEVELOPMENT OF LIPOFUSCIN IN RESPONSE TO SUSTAINED GASTRIN STIMULATION

Ageing cells, especially post-mitotic cells, are known to accumulate p igments, i.e. highly electron-dense material, referred to as ceroid or lipofuscin. This material is formed as a consequence of autophagocyto sis and peroxidation of the products undergoing degradation. The prese nt study describes the development of lipofuscin in the ECL cells of t he rat stomach. These cells produce and secrete histamine in response to gastrin. They are rich in secretory vesicles, which fuse to form va cuoles in hypergastrinaemic rats. Hypergastrinaemia was induced by con tinuous infusion of human Leu(15)-gastrin-17 for 6 days or by daily tr eatment with omeprazole for 10 weeks. Either treatment caused both vac uoles and lipofuscin bodies to appear in large numbers; the vacuoles d isappeared promptly after interruption of the hypergastrinaemia, where as the lipofuscin bodies remained. Antrectomy-evoked hypogastrinaemia was associated with a reduced number and volume density of lipofuscin bodies. Treatment with alpha-fluoromethylhistidine, an irreversible in hibitor of the histamine-forming enzyme, resulted in depletion of ECL- cell histamine and was found to prevent the omeprazole-evoked formatio n of vacuoles and lipofuscin. The numbers of both vacuoles and lipofus cin bodies were well-correlated with the serum gastrin concentration, suggesting that gastrin stimulates the development not only of vacuole s but also of lipofuscin, perhaps through enhanced autophagocytosis an d/or oxidative stress. Thus, lipofuscin bodies may develop from vacuol es, and both vacuoles and lipofuscin bodies may reflect the efforts of overstimulated ECL cells to cope with the excessive formation of secr etory products.