Introduction

The purinergic signalling hypothesis, i.e. adenosine 5’-triphosphate (ATP) as an extracellular signalling molecule [1] was not well received over the first 20 years. However, in the early 1990’s receptors for purines and pyrimidines were cloned and characterised (4 P1 adenosine receptor subtypes, 7 P2X ion channel nucleotide receptor subtypes and 8 P2Y G protein-coupled nucleotide receptors subtypes) [2]. Since then the field has flourished and much has been learned about the physiology of purinergic signalling [3]. Recent studies have focussed on the pathophysiology and therapeutic potential of purinergic signalling. For example, clopidogrel, which is widely used as an anticoagulant to treat stroke and thrombosis, has been shown to be a P2Y12 receptor antagonist acting on platelets to reduce aggregation [4]. A long acting P2Y2 receptor agonist, diquafasol, is being used to treat dry eye [5] and P1 (adenosine) receptor agonists to treat supraventricular tachycardia [6]. Recently, Afferent Pharmaceuticals has been taken over by Merck who plan to develop their P2X3 receptor antagonist for chronic cough, visceral pain and hypertension, with an investment of $1.25 billion. The potential of purinergic drugs for the treatment of osteoporosis, myocardial infarction, atherosclerosis, epilepsy, depression, bladder incontinence, inflammatory bowel disease, neurodegenerative diseases (including Alzheimer’s and Parkinson’s diseases, multiple sclerosis and amyotrophic lateral sclerosis), neuropathic pain and cancer are also being explored.

References

1. Burnstock G (1972) Purinergic nerves. Pharmacol Rev 24: 509-581. [Ref.]
2. Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50: 413-492. [Ref.]
3. Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87: 659-797. [Ref.]
4. Burnstock G, Ralevic V (2014) Purinergic signalling and blood vessels in health and disease. Pharmacol Rev 66: 102-192. [Ref.]
5. Burnstock G (2006) Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol Rev 58: 58-86. [Ref.]
6. Burnstock G, Pelleg A (2015) Cardiac purinergic signalling in health and disease. Purinergic Signal 11: 1-46. [Ref.]

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Article Information

Article Type: Opinion Article

Citation: Burnstock G (2016) Purinergic Signalling: Pathophysiology and Therapeutic Potential. J Drug Res Dev 2(4): doi http://dx.doi.org/10.16966/2470-1009.122

Copyright: © 2016 Burnstock G. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication history: 

Received date: 19 Oct 2016

Accepted date: 31 Oct 2016

Published date: 04 Nov 2016