THE PATHOBIOLOGY OF THE HUMAN ENTEROCHROMAFFIN-LIKE CELL

The significance of the enterochromaffin-like (ECL) cell as a critical endocrine regulator of gastric fundic mucosal function has only recen tly been recognized. Although the percentage of these cells present in the human fundic mucosa is less than that in rodents, the observation that they secrete histamine and are probably important modulators of parietal cell function has resulted in their attaining some considerab le biological significance. The further identification of gastrin and somatostatin receptors on the surface of the ECL cells has suggested t hat other neurohormonal influences may be significant in the regulatio n of parietal cell function, utilizing the ECL cell as an intermediate modifier. While abnormalities of ECL cells in the human stomach (hype rplasia/neoplasia) have been mostly confined to observations in patien ts with pernicious anemia and atrophic gastritis, the recent recogniti on of hyperplasia in pharmocotherapeutically induced achlorhydric or h ypochlorhydric states has excited considerable interest. It has been p roposed that the generation of luminal hypo- or achlorhydria by powerf ul acid inhibitory pharmacotherapy may result in hypergastrinemia. Thi s condition is responsible initially for the development of hyperplasi a and, subsequently, possibly even neoplasia of the ECL system of the fundic mucosa. This phenomenon seems to be prevalent in rodents but ha s so far been only rarely observed in humans, e.g., pernicious anemia, atrophic gastritis. In particular, patients with the gastrinoma compo nent of the multiple endocrine neoplasia type I syndrome exhibit ECL-c ell hyperplasia and neoplasia after exposure to acid inhibitory pharma cotherapy. It is therefore likely that an underlying genomic phenomeno n is necessary prior to the induction of hyperplasia and subsequent ne oplastic transformation. The scientific evaluation of the relationship between gastrin, ECL-cell function, and the development of hyperplasi a and neoplasia may provide some important information in regard to th e molecular evolution of gastrointestinal neuroendocrine disease state s. It is possible that the future pharmacotherapy of acid secretory di sease may require regulation not only of parietal cell but of ECL-cell function.