The CCK2 receptor antagonist, YF476, inhibits Mastomys ECL cell hyperplasia and gastric carcinoid tumor development
The CCK2 receptor antagonist, YF476, inhibits Mastomys ECL cell hyperplasia and gastric carcinoid tumor development
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DOI：
10.1016/j.regpep.2010.01.009
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发表时间：
2010-06-08
影响因子：
--
通讯作者：
Modlin, I. M.
中科院分区：
文献类型：
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作者：
Kidd, M.;Siddique, Z-L;Modlin, I. M.
YF 476是一种有效的、高选择性的苯二氮卓类胆囊收缩素2（CCK 2）受体拮抗剂。抑制棉鼠胃神经内分泌肠嗜铬样（ECL）细胞分泌、增殖和胃神经内分泌肿瘤（类癌）的自发形成。Mastomys啮齿动物种属表现出胃ECL神经内分泌肿瘤形成的遗传易感性，其可通过酸抑制和高胃泌素血症诱导而加速。在这方面，它模拟了萎缩性胃炎、高胃泌素血症和胃类癌发展的人类状况。我们研究了YF476是否可以在该模型中抑制酸抑制诱导的ECL细胞增生和瘤形成。此外，我们研究了YF476是否可以逆转已建立的ECL细胞增生和瘤形成。在Loxtidine诱导的高胃泌素血症中，靶向CCK 2受体导致ECL细胞分泌减少（血浆和粘膜组胺，以及组氨酸脱羧酶（HDC）转录物，p
YF476 is a potent and highly selective cholecystokin 2 (CCK2) receptor antagonist of the benzodiazepine class. It inhibits gastric neuroendocrine enterochromaffin-like (ECL) cell secretion, proliferation and spontaneous formation of gastric neuroendocrine tumors (carcinoids) in cotton rats. The Mastomys rodent species exhibits a genetic predisposition to gastric ECL neuroendocrine tumor formation which can be accelerated by acid suppression and induction of hypergastrinemia. In this respect, it mimics the human condition of atrophic gastritis, hypergastrinemia and gastric carcinoid development. We investigated whether YF476 could inhibit acid suppression-induced ECL cell hyperplasia and neoplasia in this model. In addition, we examined whether YF476 could reverse established ECL cell hyperplasia and neoplasia. Targeting the CCK2 receptor during Loxtidine-induced hypergastrinemia resulted in a reduction in ECL cell secretion (plasma and mucosal histamine, and histidine decarboxylase (HDC) transcripts, p