Whitehead R J, Taylor D J, Evanson J M, Hart I R, Woolley D E
Dept. of Medicine, University Hospital of South Manchester, U.K.
Biochem Biophys Res Commun. 1988 Feb 29;151(1):518-23. doi: 10.1016/0006-291x(88)90624-9.
Histamine induced a concentration-dependent increase in intracellular cyclic-AMP of the two human melanoma cell lines SK23 and DX3.LT5.1; maximal stimulation was obtained with 17.8 microM histamine which consistently produced greater than 50-fold increases in the cyclic AMP content of both cell lines. The dose-response curve for histamine in each culture was progressively displaced to the right with increasing concentrations of the histamine H2 receptor antagonist cimetidine. Ranitidine, another H2 receptor antagonist also prevented the histamine-induced cyclic AMP elevation, but the H1 receptor antagonists mepyramine and tripelennamine had no significant effect. These findings indicate that human melanoma cells express histamine H2 receptors, stimulation of which activates adenylate cyclase with a subsequent rise in intracellular cyclic AMP. Mast cell:melanoma interactions mediated by histamine in vivo might therefore be expected to modify some aspects of melanoma cell behaviour.
组胺使两种人黑素瘤细胞系SK23和DX3.LT5.1的细胞内环磷酸腺苷（cAMP）浓度依赖性增加。用17.8微摩尔组胺可获得最大刺激，两种细胞系的环磷酸腺苷含量均持续增加50倍以上。随着组胺H2受体拮抗剂西咪替丁浓度的增加，每种培养物中组胺的剂量反应曲线逐渐向右移动。另一种H2受体拮抗剂雷尼替丁也可阻止组胺诱导的环磷酸腺苷升高，但H1受体拮抗剂美吡拉敏和曲吡那敏无显著作用。这些发现表明，人黑素瘤细胞表达组胺H2受体，刺激该受体可激活腺苷酸环化酶，随后细胞内环磷酸腺苷水平升高。因此，体内由组胺介导的肥大细胞与黑素瘤的相互作用可能会改变黑素瘤细胞行为的某些方面。
