Serotonin (5-HT) at a concentration of 10(-4) to 10(-10) M impaired the cytotoxicity of human natural killer cells in whole blood. 5-HT added at the onset of the short-term cytotoxic assay had a pronounced inhibitory effect. It is very likely that the 5-HT2 receptor is involved in the inhibition of cytotoxicity because ketanserin, an inhibitor of the 5-HT2 receptor, partially prevented the effect of 5-HT. Treatment with 10(2)-10(4) IU/ml of interferon-alpha before or after the application of 5-HT decreased its inhibitory effect on the cytotoxicity. Radioligand binding studies revealed that the antagonistic effect of interferon was not due to the competition for the 5-HT2 receptors. Cycloheximide, an inhibitor of protein synthesis, did not block the suppression of natural killer activity by 5-HT, but it exerted a blocking effect on the acquisition of resistance to 5-HT induced by interferon.
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