Page 3 - 71_02

Anal. Real Acad. Nac. Farm., 2005, 71: 283-319

Revisión

Purinergic signalling: therapeutic potential *

GEOFFREY BURNSTOCK
Académico Correspondiente de la Real Academia Nacional

de Farmacia

ABSTRACT

The concept of a purinergic signalling system, using purine nucleotides and
nucleosides as extracellular messengers, was first proposed over 30 years ago.
After a brief introduction and update of purinoceptor subtypes, this article focuses
on the diverse pathophysiological roles of ATP, ADP, UTP and adenosine. These
molecules mediate short-term (acute) signalling functions in neurotransmission,
secretion and vasodilatation and long-term (chronic) signalling functions in
development, regeneration, proliferation and cell death. Plasticity of purinoceptor
expression in pathological conditions is frequently observed, including an increase
in the purinergic component of parasympathetic nervous control of the human
bladder in interstitial cystitis and outflow obstruction, and in sympathetic
cotransmitter control of blood vessels in hypertensive rats. The antithrombotic
action of clopidogrel, a P2Y12 receptor antagonist, has been shown to be particularly
useful in the prevention of recurrent strokes and heart attacks in recent clinical
trials. The role of P2X3 receptors in nociception and a novel hypothesis about
purinergic mechano-sensory transduction in visceral pain will be considered, as
well as the therapeutic potential of purinergic agonists or antagonists for the
treatment of supraventricular tachycardia, cancer, dry eye, bladder hyperactivity,
erectile dysfunction, osteoporosis, diabetes, gut motility, respiratory and vascular
disorders.

Key words: Purinoceptors.—Interstitial cystitis.—Thrombosis.—Visceral pain.—
Cancer.—Osteoporosis.—Peripheral vascular disease.—Cystic fibrosis.—Parkinson’s
disease.—Kidney failure.

* Discurso de Toma de Posesión como Académico Correspondiente de la Real Aca-
demia Nacional de Farmacia pronunciado el día 2 de diciembre de 2004.

283