NEUROHORMONAL REGULATION OF HISTAMINE-RELEASE FROM ISOLATED RABBIT FUNDIC MUCOSAL CELLS

Histamine-containing cells isolated from rabbit fundic mucosa were found in a small cell elutriation fraction (cells with diameter about 9-12 mum) enriched in mucus and endocrine cells and containing less than 1 % mast cells (F1 cells). Gastrin (HG- 1 7), pentagastrin and CCK-8 (C-terminal octapeptide of cholecystokinin) dose-dependently stimulated histamine release (EC50, respectively, 0. 1 26 +/- 0.03,0.92 +/- 0.15 and 0.21 1 +/- 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 muM). 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, 12-0-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. All these results allowed us to conclude that (i) in our cell preparation, histamine could be stored in endocrine cells (ECL cells) as its release appears to be under neurohormonal control, (ii) the muscarinic stimulation probably involves an M1-type receptor located on these cells, (iii) the phosphoinositide breakdown/protein kinase C activation pathway-plays an important role in the intracellular regulation, leading to the liberation of histamine.