Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Neuropharmacology
2010 Jun 01;587:1045-53. doi: 10.1016/j.neuropharm.2010.01.011.
Show Gene links
Show Anatomy links
Diarylamidines: high potency inhibitors of acid-sensing ion channels.
Chen X
,
Qiu L
,
Li M
,
Dürrnagel S
,
Orser BA
,
Xiong ZG
,
MacDonald JF
.
???displayArticle.abstract???
Acid-sensing ion channels (ASICs) are proton-gated cation channels that are predominantly expressed in the nervous system. ASICs are involved in a number of neurological diseases such as pain, ischemic stroke and multiple sclerosis but limited tools are available to target these channels and provide probes for their physiological functions. Here we report that the anti-protozoal diarylamidines, 4',6-diamidino-2-phenylindole (DAPI), diminazene, hydroxystilbamidine (HSB) and pentamidine potently inhibit ASIC currents in primary cultured hippocampal neurons with apparent affinities of 2.8 microM, 0.3 microM, 1.5 microM and 38 microM, respectively. These four compounds (100 microM) failed to block ENaC channels expressed in oocytes. Sub-maximal concentrations of diminazene also strongly accelerated desensitization of ASIC currents in hippocampal neurons. Diminazene blocked ASIC1a, -1b -2a, and -3 currents expressed in CHO cells with a rank order of potency 1b > 3 > 2a >or= 1a. Patchdock computational analysis suggested a binding site of diarylamidines on ASICs. This study indicates diarylamidines constitute a novel class of non-amiloride ASIC blockers and suggests that diarylamidines may be developed as therapeutic agents in treatment of ASIC-involved diseases.
Babini,
A new subunit of the epithelial Na+ channel identifies regions involved in Na+ self-inhibition.
2003, Pubmed,
Xenbase
Babini,
A new subunit of the epithelial Na+ channel identifies regions involved in Na+ self-inhibition.
2003,
Pubmed
,
Xenbase
Baraldi,
DNA minor groove binders as potential antitumor and antimicrobial agents.
2004,
Pubmed
Baron,
ASIC-like, proton-activated currents in rat hippocampal neurons.
2002,
Pubmed
Chen,
A sensory neuron-specific, proton-gated ion channel.
1998,
Pubmed
Chen,
The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity.
2005,
Pubmed
,
Xenbase
Chu,
Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels.
2004,
Pubmed
Deval,
ASIC3, a sensor of acidic and primary inflammatory pain.
2008,
Pubmed
Diochot,
A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons.
2004,
Pubmed
,
Xenbase
Dubé,
Electrophysiological and in vivo characterization of A-317567, a novel blocker of acid sensing ion channels.
2005,
Pubmed
Escoubas,
Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels.
2000,
Pubmed
,
Xenbase
Friese,
Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system.
2007,
Pubmed
Gonzales,
Pore architecture and ion sites in acid-sensing ion channels and P2X receptors.
2009,
Pubmed
Gründer,
A new member of acid-sensing ion channels from pituitary gland.
2000,
Pubmed
,
Xenbase
Hermans,
Antifungal agents used for deep-seated mycotic infections.
1983,
Pubmed
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Kellenberger,
Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure.
2002,
Pubmed
Kinabo,
Pharmacology of existing drugs for animal trypanosomiasis.
1993,
Pubmed
Krishtal,
The ASICs: signaling molecules? Modulators?
2003,
Pubmed
Kuduk,
Amiloride derived inhibitors of acid-sensing ion channel-3 (ASIC3).
2009,
Pubmed
Kuduk,
Amidine derived inhibitors of acid-sensing ion channel-3 (ASIC3).
2009,
Pubmed
Lingueglia,
Acid-sensing ion channels in sensory perception.
2007,
Pubmed
Mishra,
Chemotherapy of leishmaniasis: past, present and future.
2007,
Pubmed
Nelson,
Non-covalent ligand/DNA interactions: minor groove binding agents.
2007,
Pubmed
Paukert,
Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a.
2008,
Pubmed
,
Xenbase
Paukert,
Identification of the Ca2+ blocking site of acid-sensing ion channel (ASIC) 1: implications for channel gating.
2004,
Pubmed
,
Xenbase
Sluka,
Acid-sensing ion channels: A new target for pain and CNS diseases.
2009,
Pubmed
Sluka,
Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1.
2003,
Pubmed
Steen,
Pain due to experimental acidosis in human skin: evidence for non-adapting nociceptor excitation.
1995,
Pubmed
Ugawa,
Nafamostat mesilate reversibly blocks acid-sensing ion channel currents.
2007,
Pubmed
,
Xenbase
Ugawa,
Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors.
2002,
Pubmed
,
Xenbase
Voilley,
Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors.
2001,
Pubmed
Waldmann,
A proton-gated cation channel involved in acid-sensing.
1997,
Pubmed
,
Xenbase
Wei,
TRPM7 channels in hippocampal neurons detect levels of extracellular divalent cations.
2007,
Pubmed
Wemmie,
Acid-sensing ion channels: advances, questions and therapeutic opportunities.
2006,
Pubmed
Wilson,
Dications that target the DNA minor groove: compound design and preparation, DNA interactions, cellular distribution and biological activity.
2005,
Pubmed
Wu,
Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord.
2004,
Pubmed
Xiong,
Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases.
2008,
Pubmed
Xiong,
Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.
2004,
Pubmed
Xu,
Calcium-permeable acid-sensing ion channel in nociceptive plasticity: a new target for pain control.
2009,
Pubmed
Ziemann,
Seizure termination by acidosis depends on ASIC1a.
2008,
Pubmed
