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ASIC3

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 686

Nomenclature: ASIC3

Family: Acid-sensing (proton-gated) ion channels (ASICs)

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 531 7q36.1 ASIC3 acid sensing ion channel subunit 3
Mouse 2 530 5 A3 Asic3 acid-sensing ion channel 3
Rat 2 533 4q11 Asic3 acid sensing ion channel subunit 3
Previous and Unofficial Names Click here for help
DRASIC | TNaC1 | ACCN3 | amiloride-sensitive cation channel 3, testis | testis sodium channel 1 | acid sensing ion channel 3 | dorsal root ASIC | acid-sensing (proton-gated) ion channel 3 | acid sensing (proton gated) ion channel 3
Database Links Click here for help
Alphafold Q9UHC3 (Hs), Q6X1Y6 (Mm), O35240 (Rn)
ChEMBL Target CHEMBL5368 (Hs), CHEMBL3232696 (Mm), CHEMBL5757 (Rn)
DrugBank Target Q9UHC3 (Hs)
Ensembl Gene ENSG00000213199 (Hs), ENSMUSG00000038276 (Mm), ENSRNOG00000008380 (Rn)
Entrez Gene 9311 (Hs), 171209 (Mm), 286920 (Rn)
Human Protein Atlas ENSG00000213199 (Hs)
KEGG Gene hsa:9311 (Hs), mmu:171209 (Mm), rno:286920 (Rn)
OMIM 611741 (Hs)
Pharos Q9UHC3 (Hs)
UniProtKB Q9UHC3 (Hs), Q6X1Y6 (Mm), O35240 (Rn)
Wikipedia ASIC3 (Hs)
Functional Characteristics Click here for help
γ=13-15 pS;
biphasic response consisting of rapidly inactivating transient and sustained components;
very rapid activation (<5 ms) and inactivation (0.4 s);
fast recovery (0.4-0.6 s) @ pH 7.4, transient component partially inactivated at pH 7.2
Natural/Endogenous Ligands Click here for help
H+

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
lysophosphatidylcholine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Partial agonist 5.4 pEC50 - no 10
⤷ pEC50 5.4 (EC50 3.981x10-6 M) [10]
Not voltage dependent
Extracellular H+ Click here for species-specific activity table Ligand is endogenous in the given species Hs - ~3.5 – 6.7 pEC50 - no
⤷ pEC50 ~6.2 – 6.7 (EC50 ~6.3x10-7 – 2x10-7 M) transient component
Not voltage dependent
pEC50 ~3.5 – 4.3 (EC50 ~3.5x10-4 – 5x10-5 M) sustained component
Not voltage dependent
GMQ Small molecule or natural product Hs - ~3.0 pEC50 - no 17
⤷ pEC50 ~3.0 (EC50 ~1x10-3 M) largly non-desensitizing; at pH 7.4 [17]
Not voltage dependent
arcaine Small molecule or natural product Ligand has a PDB structure Hs - ~2.9 pEC50 - no 8
⤷ pEC50 ~2.9 (EC50 ~1.2x10-3 M) at pH 7.4 [8]
Not voltage dependent
agmatine Small molecule or natural product Ligand has a PDB structure Hs - ~2.0 pEC50 - no 8
⤷ pEC50 ~2.0 (EC50 ~9.8x10-3 M) at pH 7.4 [8]
Not voltage dependent
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
APETx2 Peptide Hs - no 7.2 pIC50 - no 4
⤷ pIC50 7.2 (IC50 6.3x10-8 M) transient component only [4]
Not voltage dependent
diminazene Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs - no ~6.5 pIC50 - no 7
⤷ pIC50 ~6.5 [7]
Not voltage dependent
A-317567 Small molecule or natural product Click here for species-specific activity table Hs - no 6.0 pIC50 - no 6
⤷ pIC50 6.0 (IC50 1.025x10-6 M) [6]
Not voltage dependent
Description: Human ASIC3 expressed in HEK293 cells
NS383 Small molecule or natural product Click here for species-specific activity table Hs - no 5.7 pIC50 - no 11
⤷ pIC50 5.7 (IC50 1.995x10-6 M) [11]
Not voltage dependent
Description: at pH6.5
nafamostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - no ~5.6 pIC50 - no 14
⤷ pIC50 ~5.6 (IC50 ~2.5x10-6 M) transient component [14]
Not voltage dependent
Ugr 9-1 Peptide Hs - no 5.0 pIC50 - no 12
⤷ pIC50 5.0 (IC50 1x10-5 M) transient component [12]
Not voltage dependent
amiloride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - no 4.2 – 4.8 pIC50 - no 16
⤷ pIC50 4.2 – 4.8 (IC50 6.3x10-5 – 1.6x10-5 M) transient component only - sustained component enhanced by 200μM amiloride at pH 4 [16]
Not voltage dependent
Gd3+ Click here for species-specific activity table Hs - no 4.4 pIC50 - no 1
⤷ pIC50 4.4 (IC50 4x10-5 M) [1]
Not voltage dependent
Zn2+ Click here for species-specific activity table Hs - no 4.2 pIC50 - no 5
⤷ pIC50 4.2 (IC50 6.1x10-5 M) [5]
Not voltage dependent
diclofenac Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs - no 4.0 pIC50 - no 15
⤷ pIC50 4.0 (IC50 9.2x10-5 M) sustained component [15]
Not voltage dependent
aspirin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs - no 4.0 pIC50 - no 15
⤷ pIC50 4.0 (IC50 9.2x10-5 M) sustained component [15]
Not voltage dependent
salicylic acid Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs - no 3.6 pIC50 - no 15
⤷ pIC50 3.6 (IC50 2.6x10-4 M) sustained component [15]
Not voltage dependent
Immunopharmacology Comments
Non-steroidal anti-inflammatory drugs (NSAIDs) are direct inhibitors of ASIC currents (reviewed in [2]). Inflammatory conditions and particular pro-inflammatory mediators such as arachidonic acid induce overexpression of ASIC-encoding genes and enhance ASIC currents [3,9,13]. The sustained current component mediated by ASIC3 is potentiated by hypertonic solutions in a manner that is synergistic with the effect of arachidonic acid [3].

References

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1. Babinski K, Catarsi S, Biagini G, Séguéla P. (2000) Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+. J Biol Chem, 275 (37): 28519-25. [PMID:10842183]

2. Baron A, Lingueglia E. (2015) Pharmacology of acid-sensing ion channels - Physiological and therapeutical perspectives. Neuropharmacology, 94: 19-35. [PMID:25613302]

3. Deval E, Noël J, Lay N, Alloui A, Diochot S, Friend V, Jodar M, Lazdunski M, Lingueglia E. (2008) ASIC3, a sensor of acidic and primary inflammatory pain. EMBO J, 27 (22): 3047-55. [PMID:18923424]

4. Diochot S, Baron A, Rash LD, Deval E, Escoubas P, Scarzello S, Salinas M, Lazdunski M. (2004) A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. EMBO J, 23 (7): 1516-25. [PMID:15044953]

5. Jiang Q, Papasian CJ, Wang JQ, Xiong ZG, Chu XP. (2010) Inhibitory regulation of acid-sensing ion channel 3 by zinc. Neuroscience, 169 (2): 574-83. [PMID:20580786]

6. Kuduk SD, Di Marco CN, Bodmer-Narkevitch V, Cook SP, Cato MJ, Jovanovska A, Urban MO, Leitl M, Sain N, Liang A et al.. (2010) Synthesis, structure-activity relationship, and pharmacological profile of analogs of the ASIC-3 inhibitor A-317567. ACS Chem Neurosci, 1 (1): 19-24. [PMID:22778804]

7. Lee JYP, Saez NJ, Cristofori-Armstrong B, Anangi R, King GF, Smith MT, Rash LD. (2018) Inhibition of acid-sensing ion channels by diminazene and APETx2 evoke partial and highly variable antihyperalgesia in a rat model of inflammatory pain. Br J Pharmacol, 175 (12): 2204-2218. [PMID:29134638]

8. Li WG, Yu Y, Zhang ZD, Cao H, Xu TL. (2010) ASIC3 channels integrate agmatine and multiple inflammatory signals through the nonproton ligand sensing domain. Mol Pain, 6: 88. [PMID:21143836]

9. Mamet J, Baron A, Lazdunski M, Voilley N. (2002) Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. J Neurosci, 22 (24): 10662-70. [PMID:12486159]

10. Marra S, Ferru-Clément R, Breuil V, Delaunay A, Christin M, Friend V, Sebille S, Cognard C, Ferreira T, Roux C et al.. (2016) Non-acidic activation of pain-related Acid-Sensing Ion Channel 3 by lipids. EMBO J, 35 (4): 414-28. [PMID:26772186]

11. Munro G, Christensen JK, Erichsen HK, Dyhring T, Demnitz J, Dam E, Ahring PK. (2016) NS383 Selectively Inhibits Acid-Sensing Ion Channels Containing 1a and 3 Subunits to Reverse Inflammatory and Neuropathic Hyperalgesia in Rats. CNS Neurosci Ther, 22 (2): 135-45. [PMID:26663905]

12. Osmakov DI, Kozlov SA, Andreev YA, Koshelev SG, Sanamyan NP, Sanamyan KE, Dyachenko IA, Bondarenko DA, Murashev AN, Mineev KS et al.. (2013) Sea anemone peptide with uncommon β-hairpin structure inhibits acid-sensing ion channel 3 (ASIC3) and reveals analgesic activity. J Biol Chem, 288 (32): 23116-27. [PMID:23801332]

13. Smith ES, Cadiou H, McNaughton PA. (2007) Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action. Neuroscience, 145 (2): 686-98. [PMID:17258862]

14. Ugawa S, Ishida Y, Ueda T, Inoue K, Nagao M, Shimada S. (2007) Nafamostat mesilate reversibly blocks acid-sensing ion channel currents. Biochem Biophys Res Commun, 363 (1): 203-8. [PMID:17826743]

15. Voilley N, de Weille J, Mamet J, Lazdunski M. (2001) Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci, 21 (20): 8026-33. [PMID:11588175]

16. Waldmann R, Bassilana F, de Weille J, Champigny G, Heurteaux C, Lazdunski M. (1997) Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons. J Biol Chem, 272 (34): 20975-8. [PMID:9261094]

17. Yu Y, Chen Z, Li WG, Cao H, Feng EG, Yu F, Liu H, Jiang H, Xu TL. (2010) A nonproton ligand sensor in the acid-sensing ion channel. Neuron, 68 (1): 61-72. [PMID:20920791]

Contributors

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