新型胆囊收缩素类似物JMV - 180、JMV - 320和JMV - 332在H345细胞中的特性研究

Characterization of the novel CCK analogs JMV-180, JMV-320, and JMV-332 in H345 cells.

作者信息

Witte D G, Nadzan A M, Martinez J, Rodriguez M, Lin C W

机构信息

Neuroscience Research Division, Abbott Laboratories, Abbott Park, IL 60064.

出版信息

Peptides. 1992 Nov-Dec;13(6):1227-32. doi: 10.1016/0196-9781(92)90033-y.

DOI:10.1016/0196-9781(92)90033-y

PMID:1337381

Abstract

The interaction of the novel CCK analogs JMV-180, JMV-320, and JMV-332 with CCK-B/gastrin receptors on small cell lung cancer (SCLC) cells was investigated. JMV-180, JMV-320, and JMV-332 potently inhibited specific binding of 125I-CCK-8 to CCK-B/gastrin receptors expressed on the SCLC cell line NCI-H345 (H345) with IC50 values of 4.9, 1.8, and 7.0 nM, respectively. JMV-320 and JMV-332 stimulated intracellular calcium ([Ca2+]i) release in a dose-dependent manner in cells preloaded with indo-1. JMV-180 did not stimulate [Ca2+]i but inhibited the [Ca2+]i release elicited by 10 nM CCK-8 in a dose-dependent manner. These data indicate that JMV-320 and JMV-332 function as CCK-B/gastrin receptor agonists while JMV-180 functions as a CCK-B/gastrin receptor antagonist in H345 cells.

摘要

研究了新型胆囊收缩素（CCK）类似物JMV - 180、JMV - 320和JMV - 332与小细胞肺癌（SCLC）细胞上CCK - B/胃泌素受体的相互作用。JMV - 180、JMV - 320和JMV - 332能有效抑制125I - CCK - 8与在SCLC细胞系NCI - H345（H345）上表达的CCK - B/胃泌素受体的特异性结合，其IC50值分别为4.9、1.8和7.0 nM。JMV - 320和JMV - 332以剂量依赖方式刺激预先加载indo - 1的细胞内钙（[Ca2+]i）释放。JMV - 180不刺激[Ca2+]i，但以剂量依赖方式抑制由10 nM CCK - 8引起的[Ca2+]i释放。这些数据表明，在H345细胞中，JMV - 320和JMV - 332作为CCK - B/胃泌素受体激动剂发挥作用，而JMV - 180作为CCK - B/胃泌素受体拮抗剂发挥作用。