gastrins and 1-oleoyl-2-acetylglycerol

Histamine-containing cells isolated from rabbit fundic mucosa were found in a small cell elutriation fraction (cells with diameter about 9-12 microns) enriched in mucus and endocrine cells and containing less than 1% mast cells (F1 cells). Gastrin (HG-17), pentagastrin and CCK-8 (C-terminal octapeptide of cholecystokinin) dose-dependently stimulated histamine release (EC50, respectively, 0.126 +/- 0.03, 0.92 +/- 0.15 and 0.211 +/- 0.025 nM) and somatostatin inhibited this release. PGE1, PGE2 and PGD2 alone were unable to enhance histamine release even at high concentrations but, when used in combination with gastrin of CCK-8, the release of histamine caused by these peptides was potentiated (about 1.5- to 2-fold). Carbachol also enhanced the liberation of histamine but with a weaker potency and efficacy than the gastrointestinal peptides (EC50: 1.50 +/- 0.06 microM). The use of specific muscarinic antagonists for M1-, M2- and M3-type receptors led us to conclude that an M1 receptor might be involved in the muscarinic-induced stimulation of histamine release. Activators of protein kinase C, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-oleyl-2-acetyl-glycerol (OAG) as well as the calcium ionophore, A23187, induced histamine release, whereas agents which increased intracellular cAMP content were devoid of effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 1-Methyl-3-isobutylxanthine; Animals; Bucladesine; Calcimycin; Carbachol; Colforsin; Diglycerides; Dose-Response Relationship, Drug; Gastric Fundus; Gastric Mucosa; Gastrins; Histamine Release; Male; Muscarinic Antagonists; Prostaglandins; Rabbits; Sincalide; Somatostatin; Tetradecanoylphorbol Acetate

Electron probe X-ray microanalysis revealed that cytoplasmic Ca2+ concentration increased in the restricted apical cytoplasm during stimulation of isolated guinea pig parietal cells with gastrin. Furthermore, this study, using 45Ca2+, aequorin and fura-2, revealed the mechanism involved in intracellular Ca2+ shifts caused by gastrin and the involvements of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol in producing those shifts. The gastrin-mediated and IP3-sensitive Ca2+ pool was located in the smooth-surfaced membrane-enriched areas and released Ca2+ in the initial phase. Gastrin-mediated Ca2+ mobilization was also evoked by diacylglycerol, comprising an intracellular Ca2+ mobilization followed by a late, sustained and more localised Ca2+ entry from the extracellular space.

Topics: Adenosine Triphosphate; Aequorin; Animals; Benzofurans; Calcimycin; Calcium; Calcium Radioisotopes; Cytoplasm; Diglycerides; Egtazic Acid; Electron Probe Microanalysis; Fluorescent Dyes; Fura-2; Gastrins; Glycerides; Guinea Pigs; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Parietal Cells, Gastric; Sugar Phosphates; Tetradecanoylphorbol Acetate