胆囊收缩素-1受体缺陷型大冢长-伊万里德岛肥胖大鼠胃酸分泌增加。

Kanagawa K, Nakamura H, Murata I, Yosikawa I, Otsuki M

Third Dept of Internal Medicine, University of Occupational and Environmental Health, Japan.

Scand J Gastroenterol. 2002 Jan;37(1):9-16. doi: 10.1080/003655202753387284.

BACKGROUND

It is hypothesized that cholecystokinin stimulates acid secretion directly and indirectly by binding to CCK-2 (CCK-B/gastrin) receptors on both parietal and enterochromaffin-like cells. At the same time, however, it inhibits acid responses by stimulating the paracrine secretion of somatostatin from D cells and thereby exerts a tonic inhibition on the parietal cells. To test the validity of this hypothesis, we determined gastric acid secretion in the CCK-1 (CCK-A) receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats.

METHODS

Gastric acid secretion was determined in the acute fistula OLETF and the control Long-Evans Tokushima Otsuka (LETO) rats. Plasma concentrations of gastrin, CCK, somatostatin and histamine were determined by radioimmunoassay. The levels of CCK-2 receptor mRNA in the mucosa of the glandular stomach were determined by Northern blot analysis.

RESULTS

Pentagastrin- and CCK-8-stimulated as well as basal acid outputs in OLETF rats were significantly higher than those in LETO rats. CCK-2 receptor antagonist reduced basal acid outputs and completely suppressed CCK-8-stimulated acid secretion in both strains. CCK-8 enhanced the pentagastrin-stimulated gastric acid output in OLETF rats, but not in LETO rats. In LETO rats, CCK-1 receptor antagonist increased CCK-8-stimulated gastric acid secretions to those in OLETF rats. The level of CCK-2 receptor mRNA in the stomach in OLETF rats was 2-fold higher than that in LETO rats. In OLETF rats, plasma concentrations of CCK and histamine were higher, whereas somatostatin concentrations were lower than those in LETO rats, with no change in basal plasma gastrin concentrations.

CONCLUSIONS

These results in the CCK-1 receptor-deficient OLETF rats confirmed that CCK stimulates acid secretion by binding to CCK-2 receptors, but at the same time inhibits acid responses by stimulating the paracrine secretion of somatostatin from D cells in the gastric mucosa.

背景

据推测，胆囊收缩素通过与壁细胞和肠嗜铬样细胞上的CCK-2（CCK-B/胃泌素）受体结合，直接或间接刺激胃酸分泌。然而，与此同时，它通过刺激D细胞旁分泌生长抑素，抑制胃酸反应，从而对壁细胞产生紧张性抑制作用。为验证这一假说的正确性，我们测定了CCK-1（CCK-A）受体缺陷型大冢长-伊文斯-德岛肥胖（OLETF）大鼠的胃酸分泌情况。

方法

测定急性瘘管OLETF大鼠和对照长-伊文斯-德岛大冢（LETO）大鼠的胃酸分泌。采用放射免疫分析法测定血浆胃泌素、CCK、生长抑素和组胺浓度。用Northern印迹分析法测定腺胃黏膜中CCK-2受体mRNA水平。

结果

OLETF大鼠中，五肽胃泌素和CCK-8刺激的以及基础胃酸分泌量显著高于LETO大鼠。CCK-2受体拮抗剂降低了基础胃酸分泌量，并完全抑制了两品系大鼠中CCK-8刺激的胃酸分泌。CCK-8增强了OLETF大鼠中五肽胃泌素刺激的胃酸分泌，但对LETO大鼠无此作用。在LETO大鼠中，CCK-1受体拮抗剂使CCK-8刺激的胃酸分泌增加至OLETF大鼠的水平。OLETF大鼠胃中CCK-2受体mRNA水平比LETO大鼠高2倍。在OLETF大鼠中，血浆CCK和组胺浓度较高，而生长抑素浓度低于LETO大鼠，基础血浆胃泌素浓度无变化。