ATP as a cotransmitter in the autonomic nervous system

Research output: Contribution to journalLiterature review

20 Citations (Scopus)

Abstract

The role of adenosine 5'-triphosphate (ATP) as a major intracellular energy source is well-established. In addition, ATP and related nucleotides have widespread extracellular actions via the ionotropic P2X receptors (ligand-gated cation channels) and metabotropic P2Y receptors (G protein-coupled receptors). Numerous experimental techniques, including myography, electrophysiology and biochemical measurement of neurotransmitter release, have been used to show that ATP has two major roles as an excitatory cotransmitter from autonomic nerves; 1) It is costored with noradrenaline in synaptic vesicles in postganglionic sympathetic nerves innervating smooth muscle preparations, such as the vas deferens and most arteries. When coreleased with noradrenaline, ATP acts at postjunctional P2X1 receptors to evoke depolarisation, Ca2+ influx, Ca2+ sensitisation and contraction. 2) ATP is also coreleased with acetylcholine from postganglionic parasympathetic nerves innervating the urinary bladder and again acts at postjunctional P2X1 receptors, and possibly also a P2X1+4 heteromer, to elicit smooth muscle contraction. In both systems the neurotransmitter actions of ATP are terminated by dephosphorylation by extracellular, membrane-bound enzymes and soluble nucleotidases released from postganglionic nerves. There are indications of an increased contribution of ATP to control of blood pressure in hypertension, but further research is needed to clarify this possibility. More promising is the upregulation of P2X receptors in dysfunctional bladder, including interstitial cystitis, idiopathic detrusor instability and overactive bladder syndrome. Consequently, these roles of ATP are of great therapeutic interest and are increasingly being targeted by pharmaceutical companies.
LanguageEnglish
Pages2-15
Number of pages14
JournalAutonomic Neuroscience: Basic and Clinical
Volume191
Early online date25 Apr 2015
DOIs
Publication statusPublished - Sep 2015

Fingerprint

Autonomic Nervous System
Adenosine Triphosphate
Purinergic P2X1 Receptors
Smooth Muscle
Neurotransmitter Agents
Norepinephrine
Nucleotidases
Urinary Bladder
Myography
Ligand-Gated Ion Channels
Interstitial Cystitis
Autonomic Pathways
Overactive Urinary Bladder
Vas Deferens
Synaptic Vesicles
Electrophysiology
Muscle Contraction
G-Protein-Coupled Receptors
Acetylcholine
Cations

Keywords

  • ATP
  • cotransmission
  • sympathetic
  • parasympathetic
  • vas deferens
  • urinary bladder
  • nucleotidase

Cite this

@article{06406f8af3ff49aaae80ebbdf462434a,
title = "ATP as a cotransmitter in the autonomic nervous system",
abstract = "The role of adenosine 5'-triphosphate (ATP) as a major intracellular energy source is well-established. In addition, ATP and related nucleotides have widespread extracellular actions via the ionotropic P2X receptors (ligand-gated cation channels) and metabotropic P2Y receptors (G protein-coupled receptors). Numerous experimental techniques, including myography, electrophysiology and biochemical measurement of neurotransmitter release, have been used to show that ATP has two major roles as an excitatory cotransmitter from autonomic nerves; 1) It is costored with noradrenaline in synaptic vesicles in postganglionic sympathetic nerves innervating smooth muscle preparations, such as the vas deferens and most arteries. When coreleased with noradrenaline, ATP acts at postjunctional P2X1 receptors to evoke depolarisation, Ca2+ influx, Ca2+ sensitisation and contraction. 2) ATP is also coreleased with acetylcholine from postganglionic parasympathetic nerves innervating the urinary bladder and again acts at postjunctional P2X1 receptors, and possibly also a P2X1+4 heteromer, to elicit smooth muscle contraction. In both systems the neurotransmitter actions of ATP are terminated by dephosphorylation by extracellular, membrane-bound enzymes and soluble nucleotidases released from postganglionic nerves. There are indications of an increased contribution of ATP to control of blood pressure in hypertension, but further research is needed to clarify this possibility. More promising is the upregulation of P2X receptors in dysfunctional bladder, including interstitial cystitis, idiopathic detrusor instability and overactive bladder syndrome. Consequently, these roles of ATP are of great therapeutic interest and are increasingly being targeted by pharmaceutical companies.",
keywords = "ATP, cotransmission, sympathetic, parasympathetic, vas deferens, urinary bladder, nucleotidase",
author = "Charles Kennedy",
year = "2015",
month = "9",
doi = "10.1016/j.autneu.2015.04.004",
language = "English",
volume = "191",
pages = "2--15",
journal = "Autonomic Neuroscience: Basic and Clinical",
issn = "1566-0702",

}

ATP as a cotransmitter in the autonomic nervous system. / Kennedy, Charles.

In: Autonomic Neuroscience: Basic and Clinical , Vol. 191, 09.2015, p. 2-15.

Research output: Contribution to journalLiterature review

TY - JOUR

T1 - ATP as a cotransmitter in the autonomic nervous system

AU - Kennedy, Charles

PY - 2015/9

Y1 - 2015/9

N2 - The role of adenosine 5'-triphosphate (ATP) as a major intracellular energy source is well-established. In addition, ATP and related nucleotides have widespread extracellular actions via the ionotropic P2X receptors (ligand-gated cation channels) and metabotropic P2Y receptors (G protein-coupled receptors). Numerous experimental techniques, including myography, electrophysiology and biochemical measurement of neurotransmitter release, have been used to show that ATP has two major roles as an excitatory cotransmitter from autonomic nerves; 1) It is costored with noradrenaline in synaptic vesicles in postganglionic sympathetic nerves innervating smooth muscle preparations, such as the vas deferens and most arteries. When coreleased with noradrenaline, ATP acts at postjunctional P2X1 receptors to evoke depolarisation, Ca2+ influx, Ca2+ sensitisation and contraction. 2) ATP is also coreleased with acetylcholine from postganglionic parasympathetic nerves innervating the urinary bladder and again acts at postjunctional P2X1 receptors, and possibly also a P2X1+4 heteromer, to elicit smooth muscle contraction. In both systems the neurotransmitter actions of ATP are terminated by dephosphorylation by extracellular, membrane-bound enzymes and soluble nucleotidases released from postganglionic nerves. There are indications of an increased contribution of ATP to control of blood pressure in hypertension, but further research is needed to clarify this possibility. More promising is the upregulation of P2X receptors in dysfunctional bladder, including interstitial cystitis, idiopathic detrusor instability and overactive bladder syndrome. Consequently, these roles of ATP are of great therapeutic interest and are increasingly being targeted by pharmaceutical companies.

AB - The role of adenosine 5'-triphosphate (ATP) as a major intracellular energy source is well-established. In addition, ATP and related nucleotides have widespread extracellular actions via the ionotropic P2X receptors (ligand-gated cation channels) and metabotropic P2Y receptors (G protein-coupled receptors). Numerous experimental techniques, including myography, electrophysiology and biochemical measurement of neurotransmitter release, have been used to show that ATP has two major roles as an excitatory cotransmitter from autonomic nerves; 1) It is costored with noradrenaline in synaptic vesicles in postganglionic sympathetic nerves innervating smooth muscle preparations, such as the vas deferens and most arteries. When coreleased with noradrenaline, ATP acts at postjunctional P2X1 receptors to evoke depolarisation, Ca2+ influx, Ca2+ sensitisation and contraction. 2) ATP is also coreleased with acetylcholine from postganglionic parasympathetic nerves innervating the urinary bladder and again acts at postjunctional P2X1 receptors, and possibly also a P2X1+4 heteromer, to elicit smooth muscle contraction. In both systems the neurotransmitter actions of ATP are terminated by dephosphorylation by extracellular, membrane-bound enzymes and soluble nucleotidases released from postganglionic nerves. There are indications of an increased contribution of ATP to control of blood pressure in hypertension, but further research is needed to clarify this possibility. More promising is the upregulation of P2X receptors in dysfunctional bladder, including interstitial cystitis, idiopathic detrusor instability and overactive bladder syndrome. Consequently, these roles of ATP are of great therapeutic interest and are increasingly being targeted by pharmaceutical companies.

KW - ATP

KW - cotransmission

KW - sympathetic

KW - parasympathetic

KW - vas deferens

KW - urinary bladder

KW - nucleotidase

UR - http://www.journals.elsevier.com/autonomic-neuroscience-basic-and-clinical

UR - http://www.autonomicneuroscience.com/article/S1566-0702%2815%2900040-5/abstract

U2 - 10.1016/j.autneu.2015.04.004

DO - 10.1016/j.autneu.2015.04.004

M3 - Literature review

VL - 191

SP - 2

EP - 15

JO - Autonomic Neuroscience: Basic and Clinical

T2 - Autonomic Neuroscience: Basic and Clinical

JF - Autonomic Neuroscience: Basic and Clinical

SN - 1566-0702

ER -