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

In previous studies me have showed that somatostatin (SST) inhibits cell di vision, mitogen-activated protein (MAP) kinase and Ras activity in the huma n 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, S STR2 or SSTR5, in these cellular events. All the analogs inhibited forskoli n-induced cAMP accumulation. Selective stimulation of SSTR1 or SSTR2 but no t of SSTR5 inhibited platelet-derived growth factor (PDGF)-induced [H-3]thy midine incorporation. The three analogs inhibited PDGF-stimulated MAP kinas e activity, at least at an early time, In contrast, none of the analogs use d individually was able to inhibit PDGF-stimulated Ras activity. A combined stimulation of SSTR2 and SSTR5 was necessary to obtain a significant inhib itory effect, suggesting the possibility of receptor heterodimerization. Th ese results indicate that SST inhibition of Ras and MAP kinase activities t akes place via different pathways and that SST inhibition of PDGF-induced c ell proliferation occurs via a Ras-independent pathway, (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.