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Glossary
- AD=
- Alzheimer disease;
- ADP=
- adenosine diphosphate;
- AMP=
- adenosine monophosphate;
- ATP=
- adenosine triphosphate;
- GABA=
- γ-aminobutyric acid;
- IL=
- interleukin;
- TRPV1=
- transient receptor potential-1.
The concept of purinergic neurotransmission was introduced in 1972 by Burnstock,1 who showed that adenosine triphosphate (ATP) mediated nonadrenergic, noncholinergic neurotransmission in autonomic nerves. Since then, it has been increasingly recognized that ATP acts as a neurotransmitter in both the peripheral and central nervous systems and is also an important transmitter of signals between different types of glial cells. The effects of ATP are mediated by various subtypes of purinergic (P)2 receptors that are widely distributed in both neurons and glial cells; ATP acts both as a fast excitatory neurotransmitter and as a neuromodulator, both directly and via its conversion to adenosine. Experimental studies indicate that ATP is involved in sensory transduction, autonomic control, synaptic modulation in both the central and peripheral nervosus systems, and neuron–glia and glia–glia interactions. ATP promotes cell proliferation, growth, and development. Not surprisingly, experimental evidence indicates that ATP may have a role in different neurologic disorders, including pain, ischemia, trauma, seizures, and inflammatory and neurodegenerative disorders. The functions of ATP as a signal among different cell groups and its potential involvement in disease have been the subject of several excellent reviews2–5 and only some key concepts are emphasized here.
ATP AS A CHEMICAL TRANSMITTER
Storage, release, and hydrolysis.
ATP and other nucleotides are taken up by and stored in both synaptic and secretory vesicles by a chloride (Cl−)-dependent vesicular nucleotide transporter that belongs to the soluble carrier (SCLC) family and is encoded by the human SLC17A gene, a member of an anion transporter family.6 There is evidence that ATP can be costored in synaptic vesicles and coreleased with other neurotransmitters by exocytosis, both in the peripheral and central nervous systems7 (table 1). For example, ATP is released together with acetylcholine from motor nerves supplying skeletal muscle and from parasympathetic terminals innervating the bladder; with norepinephrine from sympathetic terminals …
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