Purinergic signalling: past, present and future

Abstract

The discovery of non-adrenergic, non-cholinergic neurotransmission in the gut and bladder in the early 1960's is described as well as the identification of adenosine 5'-triphosphate (ATP) as a transmitter in these nerves in the early 1970's. The concept of purinergic cotransmission was formulated in 1976 and it is now recognized that ATP is a cotransmitter in all nerves in the peripheral and central nervous systems. Two families of receptors to purines were recognized in 1978, P1 (adenosine) receptors and P2 receptors sensitive to ATP and adenosine diphosphate (ADP). Cloning of these receptors in the early 1990's was a turning point in the acceptance of the purinergic signalling hypothesis and there are currently 4 subtypes of P1 receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of G protein-coupled receptors. Both short-term purinergic signalling in neurotransmission, neuromodulation and neurosecretion and long-term (trophic) purinergic signalling of cell proliferation, differentiation, motility, death in development and regeneration are recognized. There is now much known about the mechanisms underlying ATP release and extracellular breakdown by ecto-nucleotidases. The recent emphasis on purinergic neuropathology is discussed, including changes in purinergic cotransmission in development and ageing and in bladder diseases and hypertension. The involvement of neuron-glial cell interactions in various diseases of the central nervous system, including neuropathic pain, trauma and ischemia, neurodegenerative diseases, neuropsychiatric disorders and epilepsy are also considered.

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].…”

Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells

“…Extracellular ATP activates plasma membrane purinergic P2 receptors. P2 receptors are classified into two subfamilies, ionotropic P2X1-7 receptors and metabotropic P2Y1-14 receptors, and their activation regulates many physiological functions [8]. P2 receptors are also expressed in many types of cancer [9].…”

Neuroprotective roles of the P2Y2 receptor

“…Both P1 receptors for adenosine and P2 receptors (P2Rs) for adenine and/or uridine nucleotides are expressed in cells comprising the CNS and have been shown to regulate important physiological and pathophysiological functions, including neurotransmission, inflammation, cell growth, and apoptosis [11,[31][32][33]. The P2R agonist ATP is a neuro-and gliotransmitter released by exocytosis from neurons and by diffusion through hemichannels, pannexins, and voltage-gated channels in various cell types [12,17,[34][35][36][37].…”