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

immunoreactions. Recent studies have shown that P2X4 receptors
induced in spinal microglial gate tactile allodynia after nerve injury
(26) (see section on Pain). P2X7 receptors mediate superoxide
production in primary microglia and are upregulated in a transgenic
model of Alzheimers’ disease, particularly around ß-amyloid plaques.
Stimulation of microglial P2X7 receptors also leads to enhancement
of interferon-? (IFN-?)-induced type II nitric oxide synthase activity.
P2X7 receptors may therefore provide a therapeutic target for
inflammatory responses seen in neurodegenerative disorders.

P2 receptors are expressed by oligodendrocytes. However, while
P2 receptors on oligodendrocytic progenitor cells mediate increase
in [Ca2+]i, it is adenosine that appears to mediate the formation of
myelin, raising the possibility that activation of purinoceptors may
offer new approaches to the treatment of demyelinating diseases
in the CNS, such as multiple sclerosis. P2X receptors expressed by
Schwann cells may regulate the synthesis and release of cytokines
during pathophysiological events.

ONCOLOGY

The anticancer activity of adenine nucleotides was first described
by Rapaport in 1983. Intraperitoneal injection of ATP into tumour-
bearing mice resulted in significant anticancer activity against several
fast-growing aggressive carcinomas (4). ATP inhibits the growth of
murine colonic adenocarcinoma and human pancreatic carcinoma
in mice as well as inhibiting the associated weight loss. In a recent
comprehensive review about the use of ATP for the treatment of
advanced cancer (27), evidence was presented that: extracellular ATP
inhibits the growth of a variety of human tumours, including
prostate, breast, colon, liver, ovarian, colorectal, oesophageal and
melanoma cancer cells, partly by mediating apoptotic cancer cell
death; ATP administration induces resistance of non-malignant tissue
to chemo- and radiation therapy; ATP has pronounced anticachexia
effects, particularly in older patients, reducing weight loss, anorexia,
and hormonal aberrations, largely via its ability to expand blood
plasma ATP pools. It was concluded that preclinical data supporting
utilization of ATP in the treatment of advanced cancers, along with

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