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VOL. 71 (2), 283-319, 2005 PURINERGIC SIGNALLING: THERAPEUTIC POTENTIAL

It has been claimed that purinergic signalling dysfunction
(perhaps largely reduced adenosinergic activity) is involved in mania
and aggressive behaviour. Endogenous ATP has been claimed to be
involved in the regulation of anxiety via stimulation of P2Y1 receptors
in the dorsomedial hypothalamus in rats. Chronically administered
guanosine has anticonvulsant, amnesic and anxiolytic effects in mice,
perhaps associated with modulation of glutamatergic excitation.
There is a growing body of evidence suggesting that adenosine is
involved in drug addiction and withdrawal, and that purinergic
signalling pathways may offer novel targets for the therapeutic
treatment of addiction to opioids.

Multiple P2X and P2Y receptors have been identified on single
cerebellar granule cells. It has been reported that ATP continuously
modulates the cerebellar circuit by increasing the inhibitory input to
Purkinje neurons, probably via P2X5 and P2Y2 and/or P2Y4 receptor
subtypes, thus decreasing the main cerebellar output activity which
contributes to locomotor coordination.

Spinal cord traumas are a major health problem. ATP-MgCl2 has
been shown to decrease lipid peroxidation in spinal cord injury and
protect the spinal cord from secondary injury after trauma; it was
concluded that ATP-MgCl2 should be explored for the treatment of
spinal cord injuries in conjunction with other treatment modulators.

Phenylketonuria is an innervated deficiency of phenylalanine
hydroxylase activity in the liver, which leads to increased brain
levels of phenylalanine and its metabolites, leading to permanent
brain damage in the early period of postnatal brain development.
Phenylalanine has been shown to inhibit ATP diphosphohydrolase
resulting in increase in ATP levels, perhaps the neurotoxic
mechanism underlying brain damage in this disease.

Glial cells

ATP is an extracellular signalling molecule between neurones and
glia. ATP released by cellular damage and from astrocytes may be
important in triggering cellular responses to trauma and ischaemia
by initiating and maintaining reactive astrogliosis, which involves

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