Receptor-operated Ca2+ channels in gastric parietal cells: gastrin and carbachol induce Ca2+ influx in depleting intracellular Ca2+ stores

Abstract

The mechanism whereby gastrin-type receptor and muscarinic M3-type receptor regulate free intracellular Ca2+ concentration ([Ca2+]i) was studied in rabbit gastric parietal cells stimulated by either gastrin or carbachol. Both agonists induced a biphasic [Ca2+]i response: a transient [Ca2+]i rise, followed by a sustained steady state depending on extracellular Ca2+. Gastrin and carbachol also caused a rapid and transient increase in Mn2+ influx (a tracer for bivalent-cation entry). Pre-stimulation of cells with one agonist drastically decreased both [Ca2+]i increase and Mn2+ influx induced by the other. Neither diltiazem nor pertussistoxin treatment had any effect on agonist-stimulated Mn2+ entry. Thapsigargin, a Ca(2+)-pump inhibitor, induced a biphasic [Ca2+]i increase, and enhanced the rate of Mn2+ entry. Preincubation of cells with thapsigargin inhibits the [Ca2+]i increase as well as Mn2+ entry stimulated by gastrin or by carbachol. Thapsigargin induced a weak but significant increase in Ins(1,4,5)P3 content, but this agent had no effect on the agonist-evoked Ins(1,4,5)P3 response. In permeabilized parietal cells, Ins(1,4,5)P3 and caffeine caused an immediate Ca2+ release from intracellular pools, followed by a reloading of Ca2+ pools which can be prevented in the presence of thapsigargin. We conclude that (i) gastrin and carbachol mobilize common Ca2+ intracellular stores, (ii) Ca2+ permeability secondary to receptor activation involves neither a voltage-sensitive Ca2+ channel nor a GTP-binding protein from the G1 family, and (iii) agonists regulate common Ca2+ channels in depleting intracellular Ca2+ stores.

Numerous cell targets for gastrin in the guinea pig stomach revealed by gastrin/CCK B receptor localization

“…Our results are in good agreement with the previously formulated concept of GR localization in the stomach (Roche et al 1991(Roche et al , 1993Kopin et al 1992;Chiba et al 1989;Soll and Walsh 1979;Soll et al 1984;Sutliff et al 1990;Delvalle et al 1993). The presence of the same receptor in chief and parietal cells is not surprising, because these cells are derived from the same stem cell during cellular differentiation in the isthmus of the gastric gland (Gordon 1993).…”

“…In addition to stimulation of secretion, gastrin increases the flow of blood to the mucosa, is involved in contraction of muscle, and has a trophic effect on the stomach, the duodenum, and the pancreas (for a review, see Mulholland and Debas 1988). Binding studies and investigations of diverse physiological effects of gastrin have demonstrated the presence of the hormone receptor on parietal cells (Roche et al 1993;Kopin et al 1992;Chiba et al 1989;Soll and Walsh 1979;Soll et al 1984), chief cells (Sutliff et al 1990), ECL-cells (Roche et al 1991), the D-cell (Delvalle et al 1993), and muscle cells (Grider and Makhlouf 1990) of the stomach. However, a recent study involving in situ hybridization techniques has failed to detect the gastrin/CCK B receptor (GR) on all these cell types and suggests that it is present, together with the histamine, muscarinic, and dopamine receptors, on immune cells in the lamina propria of the stomach (Mezey and Palkovits 1992), a conclusion that is hotly debated (Scott et al 1993;Shanahan and Anton 1993).…”

Analysis of gastrin receptor gene expression in proliferating cells in the neck zone of gastric fundic glands using laser capture microdissection

“…Gastrin is reported to be a growth‐promoting factor for cells that express gastrin receptors [1]. We and others have shown that parietal, ECL and D cells are specific cell types that have gastrin receptors on their cell membranes [3,13,14,17,18,21–24,27]. We have also shown that ECL cells with gastrin receptors proliferate when stimulated with gastrin [9,23].…”

“…PCNA‐positive cells had the same distribution pattern as those obtained by LCM. Gastrin receptor expression is evident in ECL, parietal and D cells [3,13,14,18,21–24,27], therefore, contamination by these cells in proliferating cells obtained by LCM may have been the major cause of the pseudopositive results for gastrin receptor gene expression seen in our experiments. Indeed, we found that only 32% of the LCM‐dissected samples were free from contamination by parietal, ECL or D cells.…”

Synthesis and properties of three fluorescent derivatives of gastrin

“…The most important among these are stimulation of secretion in the stomach and growth-promoting effects on normal stomach and intestinal cells, as well as on gastrointestinal tumors. The consequences of gastrin binding to gastrin receptor-expressing cells include stimulation of cell growth [1,2], breakdown of phosphatidylinositol [3], mobilization of intracellular calcium [4,5] and activation of phospholipase C [6]. However, the mechanisms by which gastrin elicits its effects on cells are unclear.…”