GASTRIN AND CCK RECEPTORS ON HISTAMINE-CONTAINING AND SOMATOSTATIN-CONTAINING CELLS FROM RABBIT FUNDIC MUCOSA .1. CHARACTERIZATION BY MEANS OF AGONISTS

A previous study has suggested the presence of two distinct binding sites for gasrin and cholecystokinin (CCK) in isolated non-parietal cells from rabbit gastric mucosa: a receptor which binds CCK-8 and CCK-39 with a high affinity and a receptor which binds gastrin and CCK-8 with the same high affinity and CCK-39 with a lower affinity. To characterize these receptors, their ability to induce phosphoinositide breakdown was investigated. Gastrin (HG-17), CCK-39 and CCK-8 induced [H-3]inositol phosphate ([H-3]InsP) accumulation from [H-3]inositol prelabelled cells with a high potency (EC50: 0.3-2.7 nM) but CCK-8 exhibited a higher efficacy than HG-17 or CCK-39. HG-17, CCK-8 and CCK-39 induced a rapid accumulation of [H-3]inositol monophosphate ([H-3]InsP1), [H-3]inositol bisphosphate ([H-3]InsP2) and [H-3]inositol trisphosphate ([H-3]InsP3) but CCK-8 caused a two times higher accumlation than HG-17 or CCK-39. Histamine- and somatostatin-containing cells appeared to be located in this non-parietal cells population. HG-17, CCK-8 and CCK-39 dose-dependently induced histamine release with the following order of potency: HG-17 = CCK-8 (EC50 almost-equal-to 0.2 nM) > CCK-39 (EC50 almost-equal-to 4 nM). In addition, HG-17 exhibited the highest efficacy. HG-17, CCK-8 and CCK-39 enhanced somatostatin-like immunoreactivity (SLI) release with the following order of potency: CCK-8 (EC50 almost-equal-to 0.1 nM) = CCK-39 > HG-17 (EC50 almost-equal-to 10 nM); CCK-8 and CCK-39 exhibited the highest efficacy. These results led us to the following conclusions: (i) existence of a "gastrin-type" and of a "CCK-type" receptor mediating phosphoinositide breakdown in these gastric non-parietal cells. CCK-8 interacts with both receptor-types with the same affinity; (ii) the release of histamine from histamine-containing cells could be induced following "gastrin-type" receptors activation; (iii) somatostatin release from D-cells present in this non-parietal cells population could be induced following "CCK-type" receptors activation.