The exocytotic and crinophagic pathways in ECL cells of the rat stomach

Abstract: The ECL cells in the stomach produce, store and secrete a variety of secretory products, such as histamine and chromogranin A-derived peptides (e.g. pancreastatin). The functional significance of the ECL cells can be expected to reflect the nature/bioactivity of the secreted products. Although the anticipated peptide hormone of the ECL cells remains unidentified, ECL-cell histamine is recognized as an important paracrine messenger for gastric acid secretion. Based on the results of the present studies, we have classified the presumed secretory organelles of the ECL cells into the following categories: progranules, granules, secretory vesicles (immature and mature) and endocytotic microvesicles. The membrane of secretory organelles is furnished with vesicle monoamine transporter type 2, capable of accumulating histamine. The accumulation of histamine by progranules/granules appears to be associated with their transformation into large electron-lucent (but dense-cored) secretory vesicles. Mature secretory vesicles are to be found in the docking zone, i.e. close to the plasma membrane. When the ECL cell is stimulated (e.g. by gastrin), secretory vesicles in the docking zone undergo exocytosis. The process of exocytosis is coupled with endocytosis, resulting in an increased number of microvesicles in the docking zone. We suggest that progranules/granules and secretory vesicles form part of a secretory pathway which begins with Golgi-associated progranules/granules and ends with exocytosis of secretory vesicles. The actual process of exocytosis depends on a number of exocytotic proteins, many of which have been demonstrated in the ECL cells. The process of exocytosis is coupled with endocytosis and the formation of endocytotic microvesicles. When the ECL cells are excessively stimulated, secretory vesicles fuse not only with the plasma membrane but also with each other, forming large vacuoles. At the same time, lipofuscin bodies (age pigment) arise. We suggest that both vacuoles and lipofuscin bodies are manifestations of a crinophagic pathway, enabling the ECL cell to eliminate (or at least compartmentalize) superfluous secretory products