Molecular Probes for P2X7 Receptor Studies

The ionotropic P2X7 receptor (P2X7R) has become the focus of intense research interest for a number of reasons: i) it is a cation selective ion channel that is modulated by extracellular ATP. Upon stimulation by high concentrations of ATP it generates a non-selective membrane pore which is permeable...

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Main Authors: Gunosewoyo, Hendra, Coster, M., Kassiou, M.
Format: Journal Article
Published: Bentham Science Publishers 2007
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/12777
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author Gunosewoyo, Hendra
Coster, M.
Kassiou, M.
author_facet Gunosewoyo, Hendra
Coster, M.
Kassiou, M.
author_sort Gunosewoyo, Hendra
building Curtin Institutional Repository
collection Online Access
description The ionotropic P2X7 receptor (P2X7R) has become the focus of intense research interest for a number of reasons: i) it is a cation selective ion channel that is modulated by extracellular ATP. Upon stimulation by high concentrations of ATP it generates a non-selective membrane pore which is permeable to hydrophilic molecules with molecular weight up to 900 Da. ii) Though its physiological function is yet to be fully understood, there is high P2X7R expression in microglia. Importantly, this implies a pivotal role for the P2X 7R in neuro-inflammatory and -degenerative processes. In addition, P2X7R-stimulated release of traditional neurotransmitters in the brain, such as glutamate and GABA, further supports the involvement of P2X7R in neuro-inflammatory and -degenerative processes. P2X7-knockout animals are also found to be resistant to inflammation and neuropathic pain, which suggests that P2X7 antagonists could potentially serve as all-purpose analgesics. Recent advances in the development of P2X7R ligands have resulted in identification of several different classes of P2X7R antagonists, including ATP analogues (oxidized ATP), dyes (Brilliant Blue G), tyrosine derivatives (KN-62 and KN-04), cyclic imides, adamantane and benzamide derivatives. A KN-62 related radioligand has also recently been reported for use in receptor binding assays. A more extensive range of potent, selective P2X7R ligands is required for a better understanding of the cascade of cellular processes associated with the P2X 7R. This article will review P2X7R ligands discovered to date, together with their biological activity and therapeutic potential.
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spelling curtin-20.500.11937-127772017-09-13T15:02:13Z Molecular Probes for P2X7 Receptor Studies Gunosewoyo, Hendra Coster, M. Kassiou, M. KN-62 microglia purinergic tetrazoles ATP adamantyl amides antagonist P2X7 The ionotropic P2X7 receptor (P2X7R) has become the focus of intense research interest for a number of reasons: i) it is a cation selective ion channel that is modulated by extracellular ATP. Upon stimulation by high concentrations of ATP it generates a non-selective membrane pore which is permeable to hydrophilic molecules with molecular weight up to 900 Da. ii) Though its physiological function is yet to be fully understood, there is high P2X7R expression in microglia. Importantly, this implies a pivotal role for the P2X 7R in neuro-inflammatory and -degenerative processes. In addition, P2X7R-stimulated release of traditional neurotransmitters in the brain, such as glutamate and GABA, further supports the involvement of P2X7R in neuro-inflammatory and -degenerative processes. P2X7-knockout animals are also found to be resistant to inflammation and neuropathic pain, which suggests that P2X7 antagonists could potentially serve as all-purpose analgesics. Recent advances in the development of P2X7R ligands have resulted in identification of several different classes of P2X7R antagonists, including ATP analogues (oxidized ATP), dyes (Brilliant Blue G), tyrosine derivatives (KN-62 and KN-04), cyclic imides, adamantane and benzamide derivatives. A KN-62 related radioligand has also recently been reported for use in receptor binding assays. A more extensive range of potent, selective P2X7R ligands is required for a better understanding of the cascade of cellular processes associated with the P2X 7R. This article will review P2X7R ligands discovered to date, together with their biological activity and therapeutic potential. 2007 Journal Article http://hdl.handle.net/20.500.11937/12777 10.2174/092986707780831023 Bentham Science Publishers restricted
spellingShingle KN-62
microglia
purinergic
tetrazoles
ATP
adamantyl amides
antagonist
P2X7
Gunosewoyo, Hendra
Coster, M.
Kassiou, M.
Molecular Probes for P2X7 Receptor Studies
title Molecular Probes for P2X7 Receptor Studies
title_full Molecular Probes for P2X7 Receptor Studies
title_fullStr Molecular Probes for P2X7 Receptor Studies
title_full_unstemmed Molecular Probes for P2X7 Receptor Studies
title_short Molecular Probes for P2X7 Receptor Studies
title_sort molecular probes for p2x7 receptor studies
topic KN-62
microglia
purinergic
tetrazoles
ATP
adamantyl amides
antagonist
P2X7
url http://hdl.handle.net/20.500.11937/12777