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GEOFFREY BURNSTOCK AN. R. ACAD. NAC. FARM.

Infection by the parasitic blood fluke Schistosoma mansoni also
leads to thymic atrophy. The cloning and characterisation of a P2X
receptor (schP2X) from Schistosoma mansoni provides the first
example of a non-vertebrate ATP-gated ion channel and may provide
an alternative drug target for the treatment of schistosomiasis.

A novel mechanism by which ATP, probably via P2Y11 receptors,
can regulate the trafficking of specific dendritic cell populations has
been described. The migration of dendritic cells from the site of
antigen capture to lymphoid tissue is a prerequisite for the induction
and regulation of immune responses. Therefore, ATP-mediated
inhibition of migration could play an important role in inflammatory
disease and cancer. Targeting of P2Y11 receptors may provide a new
therapeutic strategy to improve the migration of dendritic cells to
induce the trafficking of antigen from the vaccine site to the draining
lymph nodes.

Allopurinal and captopril have a therapeutic effect on
granulomatous disorders, such as sarcoidosis, by a direct action
on monocyte/macrophage lineage cells partly by downregulation
of intracellular adhesion molecular-1 (ICAM-1) and P2X7 receptors.
ATP and UTP have been shown to be potent stimulators of human
haematopoietic stem cells both in vitro and in vivo. Thus, these
extracellular nucleotides may provide a novel and powerful tool to
modulate haematopoietic stem cell function to increase the number
of transplantable cells in vivo in the event of bone marrow failure.
P2X7 receptors control endocannabinoid production by microglia
cells and might constitute promising therapeutics to temper
exacerbated microinflammatory responses and allied cell damage.

MIGRAINE

Classical migraine is associated with two distinct cerebrovascular
phases; an initial vasoconstriction (not associated with pain) followed
by vasodilatation (reactive hyperaemia) associated with pain. The
“purinergic” hypothesis for migraine was originally put forward by
Burnstock in 1981 as a basis for the reactive hyperaemia and pain
during the headache phase. It was suggested that ATP and its
breakdown products adenosine 5’-monophosphate and adenosine

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