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Identification, Characterization, and Biological Activity of Somatostatin Receptors in Human Neuroblastoma Cell Lines¹

Sezione di Endocrinologia [M. M., E. B., G. F., R. L., M. S.] and Medicina Nucleare [A. B.], Dipartimento di Fisiopatologia Clinica and Clinica Medica III [F. F.], Università di Firenze, 50134 Florence; Sandoz Prodotti Farmaceutici [M. G. C.], 20135 Milan, Italy; and Molecular Genetics Section, Pediatric Branch, National Cancer Institute, National Institutes of Health, [C. J. T.], Bethesda, Maryland 20892

² To whom requests for reprints should be addressed, at Endocrinology Unit, Viale Morgagni 85, 50134 Florence, Italy.

To investigate the presence of biologically active somatostatin (SS) receptors in neural crest-derived tumors, radioligand binding studies, cyclic AMP accumulation, intracellular calcium, and growth assays were performed in eight human neuroblastoma (NB) cell lines. Mathematical modeling of binding experiments strongly indicates the presence of heterogeneity of sites. The first site (SS_R1) is present in 40% of the NB cell lines and binds with low capacity (0.5 pmol/mg protein) and high affinity (0.1–1 nM) SS14, SS28, and analogues. The second site (SS_R2) is a high capacity site (200 pmol/mg protein), widely distributed in all of the cell lines investigated, that shows relative selectivity yet low affinity (100 nM) for SS14, SS28, and [D-Trp⁸]SS14 without any apparent biological activity. SS_R1 is coupled to a pertussis toxin-sensitive G protein, inhibits forskolin- or VIP-stimulated adenylate cyclase activity, decreases intracellular free calcium, and mediates inhibition (30%) of both DNA synthesis and cell growth. Analysis of cell cycle distribution in aphidicolin-synchronized SS_R1-positive NB cells indicated that this inhibitory effect is partially mediated by a transient accumulation in G₀–G₁. Our data indicate high affinity binding sites for SS14, and analogues are present and biologically active in a subset of NB cells.

¹ Supported by grants from AIRC, Milan, Italy, and AFRCN, Florence, Italy. Also supported by a special grant (to M. M.) from SANDOZ Pharmaceuticals, Milan, Italy, and a grant from the Molecular Genetics Section, Pediatric Branch, National Cancer Institute, Bethesda, MD. G. F. was a fellowship recipient of AIRC, Milan, Italy.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 8/ 3/92. Accepted 10/28/93.

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