Potential therapeutic targets in the rapidly expanding field of purinergic signalling
Author: Burnstock G
Source: Clinical Medicine, Journal of the Royal College of Physicians
Volume 2, Number 1, 1 January 2002, pp. 45-53(9)
Clin Med. 2002 Jan-Feb;2(1):45-53.
Publisher: Royal College of Physicians
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 historical review and update of purinoceptor subtypes, this article focuses on the diverse physiological roles of adenosine triphosphate, adenosine diphosphate, uridine triphosphate and adenosine. These molecules mediate short-term (acute) signalling functions in neurotransmission, secretion and vasodilation, 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 (Plavix), a P2Y12 receptor antagonist, has been shown to be particularly promising in the prevention of recurrent strokes and heart attacks in recent clinical trials (CAPRIE and CURE). The role of P2X3 receptors in nociception and a new hypothesis concerning purinergic mechanosensory transduction in visceral pain will be considered, as will 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 and vascular disorders.
Keywords: PURINOCEPTORS; INTERSTITIAL; CYSTITIS; THROMBOSIS; VISCERAL; PAIN; CANCER; OSTEOPOROSIS; PERIPHERAL; VASCULAR; DISEASE; CYSTIC; FIBROSIS; PARKINSON'S; DISEASE; KIDNEY; FAILURE
Document Type: Research article
This page last modified
27 February, 2006
by [Content Provider]