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

treatment after verapamil pre-treatment greatly reduces the
nephrotoxic potential. The P2 receptor antagonist, PPADS, has
been shown to be an effective inhibitor of mesangial cell proliferation
in an experimental rat model of mesangial proliferative
glomerulonephritis.

In polycystic kidney disease, tubules are altered, leading to
dilated tubules or cysts encapsulated by a single monolayer of
renal epithelium. It has been postulated that autocrine purinergic
signalling may augment detrimentally cyst volume expansion,
accelerating the disease progression. An increase in expression of
P2Y2, P2Y6 and P2X7 receptors has been reported in cystic tissue
from the Han: SPRDcy/+rat model of autosomal dominant polycystic
kidney disease. P2 antagonists and inhibitors of ATP release are
being explored as therapeutic agents to treat this disease. ATP may
inhibit pathological renal cyst growth through P2X7 signalling. There
is increased glomerular expression of P2X7 receptors in two rat
models of glomerular injury due to diabetes and hypertension (22).
A further study of human and experimental glomerulonephritis also
shows increase in P2X7 receptor expression.

Administration of ATP complexed with MgCl2 has been used for
many years to improve post-ischaemic and drug-induced glomerular
and tubular function. There is convincing evidence that there is
increased sympathetic activity in renal disease, especially ischaemia.
Since ATP is established as a cotransmitter with noradrenaline in
sympathetic nerves, this may be a source of enhanced ATP in these
conditions.

NEUROLOGY

ATP is a cotransmitter in many nerve types, probably reflecting
the early evolutionary presence of purinergic signalling (23). There
is now evidence for ATP as a cotransmitter with noradrenaline (NA)
and neuropeptide Y (NPY) in sympathetic nerves, with acetylcholine
and vasoative intestinal peptide (VIP) in some parasympathetic
nerves, with nitric oxide (NO) and VIP in enteric NANC inhibititory
nerves, and with calcitonin gene-related peptide (CGRP) and
substance P in sensory-motor nerves. There is also evidence for

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