Tenidap enhances P2Z/P2X7 receptor signalling 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 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.
Sanz
J M
JM
Department of Experimental and Diagnostic Medicine, University of Ferrara, Italy.
Chiozzi
P
P
Di Virgilio
F
F
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D004357:Drug Synergism; D007211:Indoles / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D000078183:Oxindoles; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058486:Receptors, Purinergic P2X7
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D000078183:Oxindoles; C546469:P2rx7 protein, mouse; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; C062866:tenidap; D007770:L-Lactate Dehydrogenase