胆碱能、组胺能和肽能刺激对分离的人胃蛋白酶原细胞分泌胃蛋白酶原的影响。

Effects of cholinergic, histaminergic, and peptidergic stimulation on pepsinogen secretion by isolated human peptic cells.

作者信息

Lanas A I, Anderson J W, Uemura N, Hirschowitz B I

机构信息

Division of Gastroenterology, University of Alabama at Birmingham.

出版信息

Scand J Gastroenterol. 1994 Aug;29(8):678-83. doi: 10.3109/00365529409092493.

DOI:10.3109/00365529409092493

PMID:7973426

Abstract

BACKGROUND

Whereas pepsin secretion by the human stomach has been extensively investigated, the characteristics of the peptide cell cannot be fully understood from in vivo studies. We therefore studied isolated human peptic cells to test directly cellular responses to different agents.

METHODS

Eight endoscopic biopsy specimens yielded 10(6) cells, > 90% pure and > 95% viable. Secreted pepsinogen was measured with a sensitive hemoglobin digestion method at pH 2.

RESULTS

Pepsinogen secretion was concentration-dependently stimulated by acetylcholine (ACh) (EC50 = 0.3 microM), cholecystokinin (CCK)-8 (2 nM), histamine (2 microM), and gastrin-I (30 nM) but not by bombesin or pentagastrin. ACh stimulation was inhibited 40 times more potently by atropine (IC50 = 12 nM) than by pirenzepine (IC50 = 0.5 microM). Histamine was inhibited by 10(-4) cimetidine. CCK-8 stimulation was inhibited 80% by the CCK-A-selective antagonist L364,718 (IC50 = 12 nM) but not by the CCK-B-selective antagonist L365,260.

CONCLUSION

Isolated human peptic cells from endoscopic biopsy specimens secrete pepsinogen in response to ACh > CCK-8 > histamine > gastrin-I. The human peptic cell muscarinic-cholinergic receptor is not of the M1 subtype, and the CCK-8 response is predominantly mediated by a CCK-A receptor subtype.

摘要

背景

尽管对人胃中胃蛋白酶分泌已进行了广泛研究，但从体内研究尚不能完全了解肽细胞的特性。因此，我们研究了分离的人胃蛋白酶细胞，以直接测试细胞对不同试剂的反应。

方法

8份内镜活检标本获得了10⁶个细胞，纯度>90%，活力>95%。用敏感的血红蛋白消化法在pH 2条件下测量分泌的胃蛋白酶原。

结果

乙酰胆碱（ACh）（EC50 = 0.3微摩尔）、胆囊收缩素（CCK）-8（2纳摩尔）、组胺（2微摩尔）和胃泌素-I（30纳摩尔）可浓度依赖性刺激胃蛋白酶原分泌，而蛙皮素或五肽胃泌素则无此作用。阿托品（IC50 = 12纳摩尔）对ACh刺激的抑制作用比哌仑西平（IC50 = 0.5微摩尔）强40倍。组胺被10⁻⁴西咪替丁抑制。CCK-8刺激被CCK-A选择性拮抗剂L364,718（IC50 = 12纳摩尔）抑制80%，而不被CCK-B选择性拮抗剂L365,260抑制。