The effect of nucleotides on natural killer activity in mouse spleen was investigated. Adenosine ribonucleotides were found to strongly inhibit natural killer activity, with a half maximal inhibition at an ATP-concentration of 2.0 microM. The inhibition was highly specific for adenosine ribonucleotides; adenosine deoxyribonucleotides, guanosine deoxyribonucleotides, and guanosine ribonucleotides had very low, if any, inhibitory effect. Experiments with specific inhibitors showed that the effect is transmitted by purinergic receptor(s) located on the cell surface. Comparison of the kinetics of the ATP effect with the effects of trifluoperazine and quinacrine showed that ATP acts late in the lytic cycle, possibly immediately preceding the programming for lysis.
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