SIGMA(1) BINDING IN A HUMAN NEUROBLASTOMA CELL-LINE

Behaviorally, sigma, agents modulate opioid analgesia. To examine poss ible mechanisms responsible for these interactions, we have identified a cell line containing both sigma, and opioid receptors. [H-3](+)-pen tazocine binding in BE(2)-C human neuroblastoma cells is high affinity (K-D 3.4 +/- 0.7 nM) and high density (B-max 2.98 +/- 0.14 pmol/mg pr otein). Competition studies reveal a selectivity profile similar to th at of sigma, sites in guinea pig brain. (+)-Pentazocine has no effect upon either basal or forskolin-stimulated cyclase in the BE(2)-C cells , but cAMP accumulation is inhibited by the morphine, DPDPE and naloxo ne benzoylhydrazone. (+)-Pentazocine at concentrations as high as 10 m u M does not affect this opioid effect, implying that sigma(1)/opioid interactions are not mediated at the level of the cell. This suggests that their behavioral interactions result from interacting neural circ uits. Although (+)-pentazocine is without effect in the cyclase system , it does block carbachol-stimulated phosphoinositol turnover (IC50 6. 5 +/- 1.14 mu M). The specificity of the effect is confirmed by the ab ility of haloperidol (1 mu M) to shift the IC50 value of (+)-pentazoci ne 2-fold to the right.