SUPPRESSION OF NATURAL-KILLER-CELL ACTIVITY IN MOUSE SPLEEN LYMPHOCYTES BY SEVERAL DOPAMINE-RECEPTOR ANTAGONISTS

The effects of dopaminergic receptor inhibitors such as thiothixine (D -1/D-2), fluphenazine (D-1/D-2), trifluoperazine (D-1/D-2), pimozide ( D-2), flupenthixol (D-1/D-2), (+/-)-SKF 83566 (D-1), and spiperone (D- 2) on splenic natural killer (NK) cell cytotoxic activities were asses sed in vitro using mouse spleen lymphocytes or enriched NK cells. Both the activities of the splenic NK cell cytotoxicity and the effector-t arget cell conjugation were suppressed by thiothixine, fluphenazine, a nd trifluoperazine at concentrations from 2.64 to 14.78 mu M In additi on, the augmentation of the cytolytic activity of NK cells induced by interferon-alpha or interleukin-2 was antagonized by pretreatment with these neuroleptic compounds. However, neither the splenic NK cell cyt otoxicity nor the effector-target cell conjugation were affected by tr eatment with other neuroleptic compounds such as pimozide, flupenthixo l, (+/-)-SKF 83566, and spiperone. Thus, it appears that neuroleptic c ompounds such as thiothixine, fluphenazine, and trifluoperazine may ac t through the mechanisms other than a dopaminergic pathway to affect t he NK cell-target cell interaction.