Stereoselective inhibition of natural killer activity by the sigma ligand (+)-pentazocine

The effect of sigma (sigma) receptor ligands on natural killer (NK) activity was examined both in vivo and in vitro. Following injection of mice with sigma receptor ligands such as (+)-pentazocine, (-)-pentazocine, BD 1073, BD 1165 and BD 737, NK activity was measured in poly-I.C.-stimulated mouse splenocytes. (+)-Pentazocine reduced NK cell activity in a dose-dependent fashion, while the (-) enantiomer was inactive in this measure. For example, at a dose of 50 mg/kg, (+)-pentazocine suppressed NK activity (using effector to target cell ratios of 200:1, 100:1 and 50:1) by > 70%, 24 h after injection while (-)-pentazocine was inactive. The other sigma ligands examined either slightly enhanced or had no effect on NK activity. Nonetheless, parenteral administration of the sigma receptor ligand BD 1165 blocked (+)-pentazocine-induced suppression of NK activity, while the opiate receptor antagonist naltrexone was ineffective. Addition of sigma receptor ligands (10(-11)-10(-5) M) to splenocyte cultures for 24 h did not affect NK activity. These findings indicate that while sigma receptor ligands are capable of modulating NK activity, this effect is not the result of an action on splenocyte sigma receptors, but may be mediated via sigma receptors either in the central or peripheral nervous systems.