Page 31 - 71_02

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

RESPIRATORY SYSTEM

Purinergic compounds are being explored for the treatment of
cystic fibrosis, to improve the clearance of secretions from the
bronchi in chronic obstructive pulmonary disease (COPD) and for
sputum expectoration in smokers (35). The long lasting P2Y2
analogue, INS 37217, increases the duration of mucociliary clearance
and therefore has significant advantages over other P2Y2 agonists for
the treatment of cystic fibrosis. P2X4 receptors have also been
identified on lung epithelial cells and appear to be involved in
regulation of ciliary beat, manipulation of which may also be of
therapeutic benefit for cystic fibrosis. Recent evidence supports the
view that vagal afferent purinergic signalling may be involved in the
hyperactivity associated with asthma and COPD (36).

Pulmonary hypertension can be a problem in patients with COPD
which also has other causes; it is a life-threatening condition, and
intravenous ATP infusion produces a significant decrease in mean
pulmonary arterial pressure and pulmonary vascular resistance
without changing the mean systemic arterial pressure.

The use of theophylline, an adenosine-receptor antagonist, as an
antiasthmatic agent has focused attention on the development of
novel P1 receptor antagonists as asthmatic medications.

Erythromycin is a widely used antibiotic for the treatment of
upper and lower respiratory tract infections. One of the most
conspicuous effects of erythromycin is the suppression of fluid
secretion from bronchial epithelial cells in the treatment of
bronchitis. Erythromycin has been shown to block the P2X receptor-
mediated Ca2+ influx and may represent one mechanism by which it
exerts its antisecretory effects in the treatment of chronic respirator
tract infections.

The ventrolateral medulla (VLM) contains a network of
respiratory neurons that are responsible for the generation and
shaping of respiratory rhythm; it also functions as a chemoreceptive
area mediating the ventilating response to hypercapnia. Evidence
has been presented that ATP acting on P2X2 receptors expressed in
VLM neurones influences these functions. A potentially important
role for P2 receptor synaptic signalling in respiratory motor control

311