Abstract: |
Behaviorally, sigma1 agents modulate opioid analgesia. To examine possible mechanisms responsible for these interactions, we have identified a cell line containing both sigma, and opioid receptors. [3H](+)-pentazocine 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 protein). Competition studies reveal a selectivity profile similar to that 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 naloxone benzoylhydrazone. (+)- Pentazocine at concentrations as high as 10 μM does not affect this opioid effect, implying that sigma1/opioid interactions are not mediated at the level of the cell. This suggests that their behavioral interactions result from interacting neural circuits. Although (+)-pentazocine is without effect in the cyclase system, it does block carbachol-stimulated phosphoinositol turnover (IC50 6.5 ± 1.14 μM). The specificity of the effect is confirmed by the ability of haloperidol (1 μM) to shift the IC50 value of (+)- pentazocine 2-fold to the right. |
Keywords: |
human cell; binding affinity; animal; metabolism; animals; haloperidol; cell line; tumor cells, cultured; kinetics; cell culture; brain; neuroblastoma; neuroblastoma cell; drug derivative; cyclic amp; binding site; morphine; analgesics; analysis of variance; binding competition; analgesic agent; naloxone; opiate receptor; enkephalin[2,5 dextro penicillamine]; trypsin; adenylate cyclase; dissociation constant; human brain; binding, competitive; cyclazocine; n allylnormetazocine; pentazocine; receptors, sigma; naloxone benzoylhydrazone; enkephalin; ethylketazocine; opioid receptors; guinea pig; phosphatidylinositol; phosphatidylinositols; forskolin; inositol phosphate; guinea pigs; receptors, opioid; humans; human; priority journal; article; benzomorphan derivative; sus scrofa; cavia porcellus; sigma opiate receptor; enkephalins; enkephalin, d-penicillamine (2,5)-; guanylylimidodiphosphate; guanylyl imidodiphosphate; be(2)-c cells; sigma1 binding site; carbachol
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