Tenidap enhances P2Z/P2X7 receptor signalling in macrophages

Eur J Pharmacol. 1998 Aug 21;355(2-3):235-44. doi: 10.1016/s0014-2999(98)00482-8.


Tenidap is an anti-inflammatory drug whose mechanism of action is not fully understood. It has been shown to block plasma membrane anion transport and to decrease release of interleukin-1beta, probably via the inhibition of interleukin-1beta converting enzyme. In the present study we showed that: (a) tenidap increases the sensitivity of mouse macrophages to cytotoxic effects mediated by extracellular ATP; (b) tenidap increases lucifer yellow uptake through the macrophage ATP receptor; (c) pretreatment with oxidised ATP, a blocker of the P2Z/P2X7 receptor, inhibits cytotoxicity and lucifer yellow uptake due to the combined effects of ATP and tenidap; (d) macrophages lacking the P2Z/P2X7 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/P2X7 receptor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • Drug Synergism
  • Indoles / pharmacology*
  • L-Lactate Dehydrogenase / metabolism
  • Macrophages / drug effects*
  • Macrophages / physiology
  • Mice
  • Oxindoles
  • Purinergic P2 Receptor Agonists*
  • Receptors, Purinergic P2 / physiology
  • Receptors, Purinergic P2X7


  • Anti-Inflammatory Agents, Non-Steroidal
  • Indoles
  • Oxindoles
  • P2rx7 protein, mouse
  • Purinergic P2 Receptor Agonists
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate
  • tenidap
  • L-Lactate Dehydrogenase