Extracts of ECL-cell granules/vesicles and of isolated ECL cells from rat oxyntic mucosa evoke a Ca2+ second messenger response in osteoblastic cells

Surgical removal of the acid-producing part of the stomach (oxyntic mucosa) reduces bone mass through mechanisms not yet fully understood. The existen ce of an osteotropic hormone produced by the so-called ECL cells has been s uggested. These cells, which are numerous in the oxyntic mucosa, operate un der the control of circulating gastrin. Both gastrin and an extract of the oxyntic mucosa decrease blood calcium and stimulate Ca2+ uptake into bone. Conceivably, gastrin lowers blood calcium indirectly by releasing a hypothe tical hormone from the ECL cells. The present study investigated, by means of fura-2 fluorometry, the effect of extracts of preparations enriched in E CL cell granules/vesicles from rat oxyntic mucosa on mobilization of intrac ellular Ca2+ in three osteoblast-like cell lines, UMR-106.01, MC3T3-E1 and Saos-2, and of extracts of isolated ECL cells in UMR-106.01 cells. The extr acts were found to induce a dose-related rapid increase in intracellular Ca 2+ concentrations in the osteoblast-like cells. The response was not due to histamine or pancreastatin, known ECL cell constituents, and could be abol ished by pre-digesting the extracts with exo-aminopeptidase. The results sh ow that the increase in [Ca2+](i) reflects a mobilization of Ca2+ from the endoplasmic reticulum. The observation of an increase in [Ca2+](i) also in murine embryonic fibroblasts show that the response is not limited to osteo blastic cells. The finding that the extracts evoked a typical Ca2+-mediated second messenger response in osteoblastic cells provides evidence for the existence of a novel osteotropic peptide hormone (gastrocalcin), produced i n the ECL cells, and supports the view that gastrectomy-induced osteopathy may reflect a lack of this hormone. (C) 2001 Elsevier Science B.V. All righ ts reserved.