“Gastrin” and “CCK” receptors on histamine-and somatostatin-containing cells from rabbit fundic mucosa —I: Characterization by means of agonists

Abstract

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 [ 3H]-inositol phosphate ([ 3H]InsP) accumulation from [ 3H]inositol prelabelled cells with a high potency ( ec 50: 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 [ 3H]inositol monophosphate ([ 3H]InsP 1), [ 3H]inositol bisphosphate ([ 3H]InsP 2) and [ 3H]inositol trisphosphate ([ 3H]InsP 3) but CCK-8 caused a two times higher accumulation 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 ( ec 50 ≈ 0.2 nM) > CCK-39 ( ec 50 ≈ 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 ( ec 50 ≈ 0.1 nM) = CCK-39 > HG-17 ( ec 50 ≈ 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 histaminecontaining 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.