Selective stimulation of somatostatin receptor subtypes: differential effects on Ras/MAP kinase pathway and cell proliferation in human neuroblastoma cells

FEBS Letters

Nisoli, E.³  Taylor, John E.²  Vicentini, Lucia M.¹  Culler, Michael D.²  Cattaneo, Maria Grazia¹ 

[1] Department of Pharmacology, University of Milano, Via Vanvitelli 32, 20129 Milan, Italy;Biomeasure, Inc./Beaufour-IPSEN Group, Milford, MA 01757, USA;Center for Study and Research on Obesity, Department of Preclinical Sciences, LITA Vialba, L. Sacco Hospital, Via G.B. Grassi 74, 20157 Milan, Italy

关键词: Somatostatin receptor;    Somatostatin analog;    Human neuroblastoma;    Signal transduction;    Cell proliferation;   

DOI  :  10.1016/S0014-5793(00)02012-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In previous studies we have showed that somatostatin (SST) inhibits cell division, mitogen-activated protein (MAP) kinase and Ras activity in the human neuroblastoma cell line SY5Y. In the present study, we have assessed the role of a series of SST analogs, three of which were selective for SSTR1, SSTR2 or SSTR5, in these cellular events. All the analogs inhibited forskolin-induced cAMP accumulation. Selective stimulation of SSTR1 or SSTR2 but not of SSTR5 inhibited platelet-derived growth factor (PDGF)-induced [³H]thymidine incorporation. The three analogs inhibited PDGF-stimulated MAP kinase activity, at least at an early time. In contrast, none of the analogs used individually was able to inhibit PDGF-stimulated Ras activity. A combined stimulation of SSTR2 and SSTR5 was necessary to obtain a significant inhibitory effect, suggesting the possibility of receptor heterodimerization. These results indicate that SST inhibition of Ras and MAP kinase activities takes place via different pathways and that SST inhibition of PDGF-induced cell proliferation occurs via a Ras-independent pathway.

【 授权许可】

Unknown