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

synergistically with interleukin-1 to stimulate prostaglandin E2
release from human rheumatoid synovial cells. More recently, relief
of inflammatory pain by the P2X7 receptor antagonist, oxidized ATP,
in arthritic rats has been reported (19). Spinal P1 receptor activation
has been claimed to inhibit inflammation and joint destruction in
rat adjuvant-induced arthritis, supporting the view that therapeutic
strategies that target the CNS might be useful in arthritis.
Suppression of experimental Zymosan-induced arthritis by
intraperitoneal administration of adenosine has also been described.

Lymphoblastoid cells isolated from Duchenne muscular dystrophy
patients are highly sensitive to stimulation by extracellular ATP.
A recent study provides the first evidence for a role for purinergic
signalling in muscle regeneration using the mdx mouse model of
muscular dystrophy and raises the possibility of new therapeutic
strategies for the treatment of muscle disease (20). Pain related to
the musculoskeletal system (myofascial pain) is very common and
ATP has been claimed to excite or sensitize myofascial nociceptors.

NEPHROLOGY

There is a substantial presence of purinoceptors in different
regions of the nephron, the glomerulus and renal vascular system
in the kidney, including subtypes involved in the regulation of
renin secretion, glomerular filtration and the transport of water,
ions, nutrients and toxins (21). ATP and adenosine have been used
to protect kidneys from renal ischaemic-reperfusion injury, and are
being explored for the treatment of chronic renal failure and
transplantation-induced erythrocytosis. It has been proposed that
luminal P2 receptors in the nephron are part of an epithelial
«secretory» defence mechanism against bacteria or harmful particles
involved in the regulation of cell volume when transcellular solute
transport is out of balance. P2Y receptors mediate renin secretion.
ATP released from macula densa cells, serves as the major paracrine
agent mediating tabuloglomerular feedback signals to regulate
afferent arteriolar resistance.

Cyclosporine is a potent immunosuppressive agent, but its use
has been limited by the side effect of nephrotoxicity; however, ATP

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