[en] Full text: The P2X₇ purinergic receptor on B-lymphocytes is activated by extracellular ATP to form a cation selective ion channel. Receptor activation has several downstream effects including stimulation of phospholipase D (PLD), which was measured by the transphosphatidylation reaction, Chelerythrine, a protein kinase C (PKC) inhibitor at 10 μM, reduced the ATP- and PMA-induced PLD activation in B-lymphocytes by 57.7% ± 14.9 and 63,6% ± 7.3 respectively. To determine if this effect of chelerythrine on ATP-induced PLD activation was due to direct inhibition of the P2X₇ receptor or indirectly via PKC, we studied the effect of chelerythrine on ATP-induced ⁸⁶Rb⁺ efflux. ATP (0.5 mM) stimulates ⁸⁶Rb⁺ efflux at a rate of 0.36 ± 0.02 min^-1 as compared to 0.03 ± 0.01 min^-1 in the absence of ATP. Preincubation of B-lymphocytes with 10 μM chelerythrine inhibited ATP-induced ⁸⁶Rb⁺ efflux by 54.3% ± 8.8. Kinetic analysis showed a sigmoid dose response of the ⁸⁶Rb⁺ efflux with increasing concentrations of ATP consistent with allosteric activation of the receptor. Chelerythrine lowers the maximal value for ATP but had no effect on the EC₅₀. The half-maximal effective concentration for chelerythrine was 4.5 μM. Kinetic analysis suggested that chelerythrine is a non-competitive inhibitor of the PZX₇ receptor. We also examined other PKC inhibitors, stauorosporine, Ro 31-8220, GF 109203X and CPG 01251. to determine if this effect on P2X₇ receptor activation was unique to chelerythrine or shared by other PKC inhibitors. Ro 31-8220 reduced ⁸⁶Rb⁺ efflux by 64.4% ±5.1, staurosporine and one of its structural analogues, GF 109203X had less inhibitory effects (<30%). In contrast, another PKC inhibitor, CPG 01251 had no effect. The results suggest that chelerythrine has a direct inhibitory effect on the P2X₇ receptor, which is most likely due to chelerythrine binding to a site on the P2X₇ receptor itself rather than indirectly via PKC acting on the receptor. However, an additional inhibitory effect of chelerythrine on PKC downstream of the P2X₇ receptor can not be excluded