Purinergic signalling: Its unpopular beginning, its acceptance and its exciting future

Bioessays. 2012 Mar;34(3):218-25. doi: 10.1002/bies.201100130. Epub 2012 Jan 11.


Adenosine 5'-triphosphate (ATP) was identified in 1970 as the transmitter responsible for non-adrenergic, non-cholinergic neurotransmission in the gut and bladder and the term 'purinergic' was coined. Purinergic cotransmission was proposed in 1976 and ATP is now recognized as a cotransmitter in all nerves in the peripheral and central nervous systems. P1 (adenosine) and P2 (ATP) receptors were distinguished in 1978. Cloning of these receptors in the early 1990s was a turning point in the acceptance of the purinergic signalling hypothesis. There are both short-term purinergic signalling in neurotransmission, neuromodulation and secretion and long-term (trophic) purinergic signalling of cell proliferation, differentiation and death in development and regeneration. Much is known about the mechanisms of ATP release and its breakdown by ectonucleotidases. Recently, there has been emphasis on purinergic pathophysiology, including neurodegenerative and neuropsychiatric disorders. Purinergic therapeutic strategies are being developed for treatment of gut, kidney, bladder, lung, skeletal and reproductive system disorders, pain and cancer.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Animals
  • Humans
  • Ion Channels / chemistry
  • Nervous System / chemistry
  • Neurodegenerative Diseases / therapy
  • Neurotransmitter Agents / chemistry*
  • Neurotransmitter Agents / pharmacology
  • Peripheral Nervous System / chemistry
  • Purinergic P2 Receptor Agonists / chemistry
  • Purines / chemistry
  • Pyrimidines / chemistry
  • Receptors, Purinergic / chemistry*
  • Receptors, Purinergic P2X / chemistry
  • Synaptic Transmission*


  • Ion Channels
  • Neurotransmitter Agents
  • Purinergic P2 Receptor Agonists
  • Purines
  • Pyrimidines
  • Receptors, Purinergic
  • Receptors, Purinergic P2X
  • Adenosine Triphosphate
  • pyrimidine