TENIDAP ENHANCES P2Z P2X(7) RECEPTOR SIGNALING IN MACROPHAGES/

Tenidap is an anti-inflammatory drug whose mechanism of action is not fully understood. It has been shown to block plasma membrane anion tra nsport and to decrease release of interleukin-1 beta, probably via the inhibition of interleukin-1 beta converting enzyme. In the present st udy we showed that: (a) tenidap increases the sensitivity of mouse mac rophages to cytotoxic effects mediated by extracellular ATP; (b) tenid ap increases lucifer yellow uptake through the macrophage ATP receptor ; (c) pretreatment with oxidised ATP, a blocker of the P2Z/P2X(7) rece ptor, inhibits cytotoxicity and lucifer yellow uptake due to the combi ned effects of ATP and tenidap; (d) macrophages lacking the P2Z/P2X(7) receptor are resistant to the synergistic effect of tenidap and ATP. The results suggest that tenidap synergises with extracellular ATP for activation of the P2Z/P2X(7) receptor. (C) 1998 Elsevier Science B.V. All rights reserved.