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

be useful for the treatment of neurogenic bladder dysfunction. Drugs
that alter ATP release or breakdown might also be therapeutic
targets. Expression of P2 receptors in bladder urethelium, as well as
nerve and smooth muscle, changes in a cat model of interstitial
cystitis and may be linked with painful bladder symptoms.

Normal penile erectile function is dependent upon a delicate
balance between contracting and relaxing factors in the corpus
cavernosum smooth muscle, which are modulated by signalling
from both nerves and endothelial cells. Evidence has accumulated
to support a pivotal role for non-adrenergic, non-cholinergic
neurotransmitters. NO plays a central role in mediating cavernosal
smooth muscle relaxation, but other neurotransmitters can modulate
this action and may play a role in erectile dysfunction. ATP potently
relaxes cavernosal smooth muscle strips in vitro, an action
pharmacologically consistent with P2Y receptors. Indeed, P2Y
receptors are present on both cavernosal smooth muscle cells and
endothelial cells, and ATP is released from a subpopulation of the
cavernosal nerves. It appears that smooth muscle relaxation is caused
both by ATP acting directly on the cavernosal smooth muscle cells
and indirectly, mediated by NO released from the endothelial cells.
ATP-mediated cavernosal relaxation is impaired in diabetes mellitus
(independent of NO) implying that purinergic signalling may be
involved in the pathophysiology of erectile dysfunction.

In humans, ATP induces a significant increase in sperm fertilizing
potential and this provides a rationale for the use of ATP for treatment
of spermatozoa during in vitro fertilization. Knockout mice lacking
P2X1 receptors appear normal, but fail to breed and this is associated
with loss of the purinergic component of sympathetic cotransmissin
in the vas deferens; these findings raise the possibility of developing
non-hormonal ways of regulating male fertility. Differential, stage-
dependent immunostaining for P2X receptors during spermatogenesis
in the adult rat testes has been described (42) and opens up the
possibility of purinergic targets for both fertility and contraception.
Evidence has been presented that glyolysis has an unexpectedly
important role in providing the ATP required for sperm motility
throughout the length of the sperm flagellum.

The potential role of P2X3 receptors in mechanosensory
transduction has already been mentioned in relation to the bladder

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