Expression of the calcium-sensing receptor on human antral gastrin cells in culture.

Abstract

The presence of the extracellular calcium-sensing receptor on human antral gastrin cells was investigated. Reverse transcription PCR using mRNA isolated from gastrin cellenriched cell cultures identified a product with a sequence identical to part of the human parathyroid-secreting cell calcium-sensing receptor. Immunocytochemistry with an antibody to the extracellular region of the receptor immunostained all gastrin cells (but not mucin or somatostatin cells), and detected appropriate-sized bands in Western blots of whole cell lysates. Increasing extracellular calcium levels from 0.5 to 9 mM stimulated gastrin release in a concentrationdependent manner, with maximal release obtained at 7.2 mM. A known agonist of the calcium receptor, spermine also stimulated gastrin release. Microfluorimetry of identified gastrin cells demonstrated that increasing extracellular calcium resulted in an initial rapid rise in intracellular calcium followed by a plateau level that returned to basal levels immediately after removal of the elevated calcium. The traces were consistent with activation of a receptor-mediated mechanism rather than a concentration-dependent influx of calcium. In conclusion, these data indicate that G cells express the calcium-sensing receptor, and that activation of the receptor may explain the acid rebound phenomenon associated with calcium-containing antacid preparations.

Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion

“…The cell surface pattern of immunofluorescence was consistent with the expected membranous distribution of cell surface receptors. The presence of the receptor at both the apical and basolateral cell surfaces agrees with previous reports (16) and supports the potential for sensing ligands from both the gastric lumen as well as the serum. The G-cell specificity for CaR immunofluorescence was confirmed by specific colocalized gastrin immunofluorescence and the lack of CaR immunofluorescence in CaR-null littermates and in the absence of primary antibody (Fig.…”

“…Although G-cell CaR expression and CaR-dependent response to extracellular Ca 2+ (8,16) suggest a direct chemosensory role, they do not preclude a role for neuronal CaR indirectly regulating the G cell. In fact, the rat gastric submucosal and myenteric neurons express CaR (9).…”

Immunocytochemical Localization of the Extracellular Calcium-Sensing Receptor in Normal and Malignant Human Large Intestinal Mucosa

“…Our immunohistochemical data reveal that in normal mucosa the CaR is present exclusively in cells at the crypt base that could be charac- terized as chromogranin A-positive enteroendocrine cells. This is consistent with a report from Ray et al (1997), who were able to localize the CaR in human antral endocrine cell-enriched cultures to gastrin-but not to somatostatin-producing cells. It should be noted that the frequency of chromogranin A-reactive endocrine cells in the human gastrointestinal tract is highest, apart from the proximal duodenum, in the distal colon and rectum (Facer et al 1989).…”

pH Sensing by the Calcium-sensing Receptor

“…For acid-secreting organs such as the stomach and the kidney, the CaR will probably experience the alkaline tide associated with acid secretion from the apical membrane. In the stomach, the CaR is expressed in G (gastrinsecreting) cells as well as the acid-secreting gastric parietal cells, in which activation of the CaR seems to be associated with acid secretion (27)(28)(29). The alkalinization of the interstitial fluid adjacent to the basolateral membrane could lead to facilitation of acid secretion under conditions in which local Ca 2ϩ may remain largely unchanged.…”