Iwata N, Murayama T, Matsumori Y, Ito M, Nagata A, Taniguchi T, Chihara K, Matsuo Y, Minowada J, Matsui T
Department of Medicine, Kobe University School of Medicine, Japan.
Blood. 1996 Oct 1;88(7):2683-9.
The cholecystokinin (CCK)-B/gastrin receptor binds two brain-gut hormones, CCK and gastrin, with high affinities. These peptides have a trophic effect on gastrointestinal cells expressing the receptor in vivo as well as in vitro. Recently, this receptor mRNA was reported to be expressed in immunocytes localized in the lamina propria of normal rat stomach mucosa. Here, we studied the receptor expression in human hematopoietic cells in order to determine whether they play a role in cell growth. The CCK-B/gastrin receptor mRNA was detectable in the polymorphonuclear (PMN) cells but not in the mononuclear cells of normal peripheral white blood cells by reverse transcription-polymerase chain reaction. The receptor transcript was, however, expressed in human leukemia cell lines (14 of 18 cell lines tested) derived from not only myeloid, but also T- and B- lymphoid lineages. The CCK-B/gastrin receptors on several leukemia cell lines were shown to be biologically active by demonstrating ligand-dependent cell proliferation in serum-deprived medium. Interestingly, a human CCK-B/gastrin receptor specific antagonist, YM022, but not its stereotype isoform, selectively inhibited the DNA synthesis of THP-1, MOLT-16, MOLT-14, and CCRF-CEM in the absence of exogenous peptide ligands. Further investigation revealed that these leukemia cell lines and normal PMN cells also expressed gastrin mRNA. These results suggest that growth of human leukemia cells is promoted by an autocrine mechanism through the CCK-B/gastrin receptors.
胆囊收缩素（CCK）-B/胃泌素受体以高亲和力结合两种脑肠肽，即CCK和胃泌素。这些肽在体内和体外对表达该受体的胃肠道细胞具有营养作用。最近，据报道该受体mRNA在正常大鼠胃黏膜固有层中的免疫细胞中表达。在此，我们研究了人造血细胞中的受体表达，以确定它们是否在细胞生长中发挥作用。通过逆转录-聚合酶链反应，在正常外周血白细胞的多形核（PMN）细胞中可检测到CCK-B/胃泌素受体mRNA，而在单核细胞中未检测到。然而，该受体转录本在源自髓系以及T和B淋巴系的人白血病细胞系（18个测试细胞系中的14个）中表达。通过在无血清培养基中证明配体依赖性细胞增殖，表明几种白血病细胞系上的CCK-B/胃泌素受体具有生物学活性。有趣的是，一种人CCK-B/胃泌素受体特异性拮抗剂YM022，而非其构象异构体，在无外源性肽配体的情况下选择性抑制THP-1、MOLT-16、MOLT-14和CCRF-CEM的DNA合成。进一步研究发现，这些白血病细胞系和正常PMN细胞也表达胃泌素mRNA。这些结果表明，人白血病细胞的生长通过CCK-B/胃泌素受体以自分泌机制促进。
