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

There is increasing interest in the therapeutic potential of
purinergic compounds in a wide range of disease conditions both in
relation to P1 and P2 receptors. A number of purine-related
compounds have been patented. The autonomic nervous system
shows marked plasticity. Dramatic changes occur in the expression
of cotransmitters and receptors during development and ageing,
in nerves that remain after trauma or surgery and in disease
conditions. There are several pathological conditions in which the
cotransmission of purinergic components is increased. Readers are
referred to recent reviews about the therapeutic potential of
purinergic signalling (3, 4). Some of the statements made in this
article are not supported by more recent reports because a limit of
40 references has been stipulated.

CARDIOVASCULAR SYSTEM

Adenosine and ATP are very much involved in the mechanisms
underlying local control of vessel tone as well as cell migration,
proliferation, differentiation and death during angiogenesis,
atherosclerosis and restenosis following angioplasty (5). ATP,
released as a cotransmitter from sympathetic nerves, constricts
vascular smooth muscle via P2X receptors, while ATP released from
sensory-motor nerves during «axon reflex» activity dilates vessels via
P2Y receptors. Further, ATP released from endothelial cells during
changes in flow (shear stress) or hypoxia acts on P2Y receptors in
endothelial cells to release nitric oxide (NO) resulting in relaxation.
Adenosine, produced by the breakdown of extracellular ATP, causes
vasodilatation via smooth muscle P1 receptors. P2X receptors are
also present on endothelial cells and appear to be associated with
cell adhesion and permeability.

There have been very promising developments concerning
purinergic antithrombotic drugs. Platelets are known to express both
P2Y1 P2Y12 and P2X1 receptors. «Mega» clinical trials (CAPRIE
and CURE) have provided clear evidence that the purinergic
antithrombotic drugs clopidogrel and ticlopidine, which are
antagonists to the platelet P2Y12 receptor, reduce the risks of
recurrent strokes and heart attacks, especially when combined with

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