Unresolved issues and controversies in purinergic signalling

Some areas of current interest in the rapidly expanding purinergic signalling field that are controversial or are unresolved are highlighted in this review. These include the mechanisms underlying: ATP transport across cell and vesicle membranes; the interaction of multiple receptors for purines and pyrimidines on single cells; the blocking effect of antagonists to P2X(4) and P2X(7) receptors expressed by microglial cells in neuropathic and inflammatory pain; and the complex actions mediated by P2X(7) receptors. Some desirable areas for further research are also discussed including: comparative studies of the evolution of purinergic signalling; studies of purinergic signalling in development and regeneration, including the involvement of stem cells; behavioural studies; and therapeutic strategies.