CYTOLYTIC P2X PURINOCEPTORS

Anedoctal evidence accumulated over almost 20 years has shown that man y different cell types are killed by sustained exposure to high concen trations of extracellular ATP, The plasma membrane receptors involved have been pharmacologically characterized and cloned during the last 3 years, and named purinergic P2X, P2X receptors share an intriguing st ructural relatedness with Caenorhabditis elegans degenerins and mammal ian amiloride-sensitive Na channels (ENaCs), Depending on the ATP dose , length of stimulation and receptor subtype, P2X receptor stimulation may cause necrosis or apoptosis, The intracellular pathways activated are poorly known, but the perturbation in intracellular ion homeostas is clearly plays a major role, ICE proteases (caspases) are also trigg ered, nonetheless their activation is not requested for ATP-dependent cell death, The physiological meaning of P2X receptor-dependent cytoto xicity is not understood, but an involvement in immune-mediated reacti ons is postulated.