Somatostatin possesses antlsecretory and antiproliferative activity on some human tumors. We herein report that, in a human neuroblastoma cell line, the somatostatin analogue BIM 23014 inhibited mitogen-activated protein (MAP) kinase activity stimulated by either insulin-like growth factor-l, whose receptor bears a tyrosine kinase, or carbachol, which acts at a G-protein coupled receptor. In a human small cell lung carcinoma line BIM inhibited serum-stimulated MAP kinase activation. These inhibitory actions occur in a dose range quite similar to that observed for suppression of proliferation induced by the analogue in the same cell lines. The decrease in CAMP elicited by the analogue in the two cell lines is not responsible for its inhibitory action on MAP kinase and cell growth. Moreover, the analogue did not modify intracellular [Ca*+] and pH. An involvement of a phosphatase activity is suggested.

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Radioligand binding assays and functional experiments revealed that the SK-N-BE neuroblastoma cell line expresses a similar ratio of~t-and 6-opioid receptors, both negatively coupled to adenylyl cyclase through pertussis toxin-sensitive G proteins. Our findings also indicate that some functional interaction occurred between the two opioid subtypes; in fact, long-term exposure to [D-A1a 2-N-methyl-Phe4-Gly-ol 5] enkephalin (DAMGO), ã .t-selective agonist, sensitized the functional response of the 6-selective agonist but not vice versa. It is interesting that in acute interaction experiments, we observed a shift to the right of the concentration-effect curve of either DAMGO or ED-Pen25] enkephalin (DPDPE), a 6-selective agonist, as a result of DPDPE or DAMGO administration, respectively. In addition, low doses of naloxone, an antagonist selective for~.treceptors, increased the inhibitory effect of [D-Ala2,D-Met5] enkephalinamide (DAME), a mixed~i/6 agonist, on adenylyl cyclase activity. Taken overall, these data support the hypothesis of the existence of a cross talk between~t and 6 receptors in the SK-N-BE cell line. Key Words: Neuroblastoma cell linesbtand 6-opiold receptors-Functional interaction -Adenylyl cyclase activity.

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