BIOCHEMICAL-EVIDENCE OF FUNCTIONAL INTERACTION BETWEEN MU-OPIOID AND DELTA-OPIOID RECEPTORS IN SK-N-BE NEUROBLASTOMA CELL-LINE

Radioligand binding assays and functional experiments revealed that th e SK-N-BE neuroblastoma cell line expresses a similar ratio of mu- and delta-opioid receptors, both negatively coupled to adenylyl cyclase t hrough pertussis toxin-sensitive G proteins. Our Findings also indicat e that some functional interaction occurred between the two opioid sub types; in fact, long-term exposure to [D-Ala(2)-N-methyl-Phe(4)-Gly-ol (5)] enkephalin (DAMGO), a mu-selective agonist, sensitized the functi onal response of the delta-selective agonist but not vice versa, It is interesting that in acute interaction experiments, we observed a shif t to the fight of the concentration-effect curve of either DAMGO or [D -Pen(2,5)]enkephalin (DPDPE), a delta-selective agonist, as a result o f DPDPE or DAMGO administration, respectively, In addition, low doses of naloxone, an antagonist selective for mu receptors, increased the i nhibitory effect of [D-Ala(2),D-Met(5)] enkephalinamide (DAME), a mixe d mu/delta agonist, on adenylyl cyclase activity. Taken overall, these data support the hypothesis of the existence of a cross talk between mu and delta receptors in the SK-N-BE cell line.