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

Abstract

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.

Distribution of purinergic P2X receptors in the equine digit, cervical spinal cord and dorsal root ganglia

“…3 Immunostaining for P2X 1 (a, e), P2X 2 (b, f), P2X 3 (c, g) and P2X 7 to enable it to function in its roles within the suspensory apparatus of the distal phalanx in equids [22]. Previous studies in human and rat skin keratinocytes have reported the presence of P2X 2 , P2X 3 , P2X 5 and P2X 7 receptor subunits [23,24]. P2X receptors found in the skin are suggested to have an important physiological role as an initial sensor for external stimuli, and P2X 7 receptors, known to be involved in ATP-induced apoptosis, are likely to participate in the process of the end-stage terminal differentiation of keratinocytes [23].…”

Purinergic control of lysenin’s transport and voltage-gating properties

“…Neurotransmission, secretion, transduction, cell proliferation, motility, and differentiation are typical examples of biological functions modulated by nucleotides or nucleosides acting as extracellular signaling molecules [5][6][7][8][9][10][11]. Burnstock's early hypothesis that ATP, the major intracellular molecule providing the energy required for multiple biochemical and biophysical processes, may actually function as an extracellular non-adrenergic and noncholinergic signaling molecule [12,13] was received with great skepticism [14,15]. After several decades of extensive work, the scientific community came to the realization that ATP is widely employed as a signaling molecule in multiple biological processes in both normal and pathophysiological conditions [9,11,[16][17][18][19][20][21][22][23][24].…”

Roles of extracellular nucleotides and P2 receptors in ectodomain shedding

“…P2X and P2Y activation stimulates various downstream signalling pathways that affect many cellular processes. Although these pathways remain to be fully elucidated, it is widely accepted that purinergic signalling is involved in physiological and pathophysiological responses including neurotransmission, coagulation, inflammation, tissue regeneration, and cell proliferation, differentiation and death [7].…”