Top ▲

5-HT3A

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 379

Nomenclature: 5-HT3A

Family: 5-HT3 receptors

Contents:

Quaternary Structure: Subunits
5-HT3A
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure of the mouse serotonin 5-HT3 receptor
PDB Id:  4PIR
Resolution:  3.5Å
Species:  Mouse
References:  21
Functional Characteristics Click here for help
γ = 0.4-0.8 pS [+ 5-HT3B, γ = 16 pS]; inwardly rectifying current [+ 5-HT3B, rectification reduced]; nH 2-3 [+ 5-HT3B 1-2]; relative permeability to divalent cations reduced by co-expression of the 5-HT3B subunit
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  Rb+ = Cs+ = Li+ > Na+ > Ca2+ > Mg2+
References:  41
Species:  Human Mouse
Single channel conductance (pS):  0.3-1.0 0.4-0.6
References:  6,19,41 17,30
Species:  Human
Single channel current rectification:  Inward
References:  6
Species:  Human Mouse
Macroscopic current rectification:  Inward Inward
References:  6,19,41 17,30
Ion Selectivity and Conductance Comments
For the human receptor PCa/PCs = 1.0-1.4 [6,12,36] and PMg/PCs = 0.41-0.61 [6,12]. The fractional calcium flux (Ca2+ Pf) is 4.1% [45].
Natural/Endogenous Ligands Click here for help
Ca2+
5-hydroxytryptamine
Mg2+
Zn2+

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]meta-chlorophenylbiguanide Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Partial agonist 9.0 pKd 43
⤷ pKd 9.0 [43]
quipazine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 9.5 pKi 5
⤷ pKi 9.5 [5]
meta-chlorphenylbiguanide Small molecule or natural product Rn Agonist 9.0 pKi 39,43
⤷ pKi 9.0 [39,43]
CSTI-300 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 8.6 pKi 48
⤷ pKi 8.6 (Ki 2.26x10-9 M) [48]
meta-chlorphenylbiguanide Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.6 – 7.2 pKi 5,24,31,34,39
⤷ pKi 6.6 – 7.2 [5,24,31,34,39]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 6.5 – 6.9 pKi 5,24,31,34
⤷ pKi 6.5 – 6.9 [5,24,31,34]
2-methyl-5-HT Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.0 – 6.7 pKi 24,31,34,39
⤷ pKi 6.0 – 6.7 [24,31,34,39]
1-phenylbiguanide Small molecule or natural product Mm Partial agonist 6.2 pKi 4
⤷ pKi 6.2 [4]
1-phenylbiguanide Small molecule or natural product Click here for species-specific activity table Hs Agonist 4.7 – 5.6 pKi 4-5,24,34,39
⤷ pKi 4.7 – 5.6 [4-5,24,34,39]
meta-chlorphenylbiguanide Small molecule or natural product Rn Agonist 6.7 – 6.9 pEC50 37,40
⤷ pEC50 6.7 – 6.9 [37,40]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 5.5 – 6.4 pEC50 3,8,12,15,34,39,50
⤷ pEC50 5.5 – 6.4 [3,8,12,15,34,39,50]
meta-chlorphenylbiguanide Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.4 – 5.8 pEC50 3,12,34,39-40
⤷ pEC50 5.4 – 5.8 (EC50 4x10-6 – 1.6x10-6 M) [3,12,34,39-40]
2-methyl-5-HT Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.5 – 5.6 pEC50 3,12,34,39
⤷ pEC50 5.5 – 5.6 (EC50 3.1x10-6 – 2.5x10-6 M) [3,12,34,39]
SR57227A Small molecule or natural product Rn Agonist 5.4 pEC50 16
⤷ pEC50 5.4 (EC50 3.6x10-6 M) [16]
1-phenylbiguanide Small molecule or natural product Mm Partial agonist 4.5 pEC50 14
⤷ pEC50 4.5 [14]
1-phenylbiguanide Small molecule or natural product Click here for species-specific activity table Hs Agonist 4.1 pEC50 3
⤷ pEC50 4.1 (EC50 8x10-5 M) [3]
View species-specific agonist tables
Agonist Comments
Apparent affinities of agonists are for ligand binding to the recombinant 5-HT3A receptor expressed in mammalian cells, or pEC50 values determined under voltage-clamp for the receptor expressed in Xenopus laevis oocytes. Selectivity refers to the 5-HT3 receptor family: the agents listed do not discriminate between 5-HT3A and 5-HT3AB receptors, although their affinities/potencies at the latter are in some cases lower. Comments concerning efficacy relate to data obtained from voltage-clamp studies of, where possible, the relevant species orthologues of 5-HT3A receptor expressed in Xenopus laevis oocytes [3,37,50]. Where significant species differences in agonist potency exist, data for rat and mouse orthologues of the receptor are also listed.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]ramosetron Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.8 pKd 39
⤷ pKd 9.8 (Kd 1.5x10-10 M) [39]
[3H]GR65630 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.6 – 9.3 pKd 23,34
⤷ pKd 8.6 – 9.3 (Kd 2.56x10-9 – 4.8x10-10 M) [23,34]
[3H]granisetron Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.9 pKd 5,24
⤷ pKd 8.9 (Kd 1.2x10-9 M) [5,24]
[3H](S)-zacopride Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.7 pKd 46
⤷ pKd 8.7 (Kd 2x10-9 M) [46]
[3H]LY278584 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.5 pKd 1
⤷ pKd 8.5 (Kd 3.08x10-9 M) [1]
palonosetron Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Antagonist 10.5 pKi 42
⤷ pKi 10.5 (Ki 3.2x10-11 M) [42]
ramosetron Small molecule or natural product Hs Antagonist 10.0 pKi 23
⤷ pKi 10.0 [23]
alosetron Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Antagonist 9.5 pKi 23
⤷ pKi 9.5 (Ki 3.16x10-10 M) [23]
cilansetron Small molecule or natural product Hs Antagonist 9.3 pKi 23
⤷ pKi 9.3 [23]
(S)-zacopride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.0 pKi 5
⤷ pKi 9.0 (Ki 1x10-9 M) [5]
granisetron Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist ~8.6 – 8.8 pKi 24,39
⤷ pKi ~8.6 – 8.8 (Ki ~2.5x10-9 – 1.5x10-9 M) [24,39]
tropisetron Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.5 – 8.8 pKi 34,39
⤷ pKi 8.5 – 8.8 (Ki 3x10-9 – 1.5x10-9 M) [34,39]
azasetron Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.5 pKi 5
⤷ pKi 8.5 [5]
vortioxetine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 8.4 pKi 2
⤷ pKi 8.4 (Ki 3.7x10-9 M) [2]
ricasetron Small molecule or natural product Hs Antagonist 8.2 pKi 5
⤷ pKi 8.2 [5]
ondansetron Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist ~7.8 – 8.3 pKi 5,24,39
⤷ pKi ~7.8 – 8.3 (Ki ~1.5x10-8 – 5x10-9 M) [5,24,39]
AZD0328 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 pKi 38
⤷ pKi 7.9 (Ki 1.2x10-8 M) [38]
(R)-zacopride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 pKi 5
⤷ pKi 7.9 [5]
tubocurarine Small molecule or natural product Approved drug Mm Antagonist 6.6 – 7.1 pKi 4,55
⤷ pKi 6.6 – 7.1 [4,55]
metoclopramide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.0 – 6.4 pKi 5,24
⤷ pKi 6.0 – 6.4 (Ki 1.03x10-6 – 3.54x10-7 M) [5,24]
cocaine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.1 – 5.4 pKi 5,24
⤷ pKi 5.1 – 5.4 [5,24]
tubocurarine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 4.8 pKi 5,24
⤷ pKi 4.8 [5,24]
View species-specific antagonist tables
Antagonist Comments
Data tabulated are for ligand binding to the recombinant 5-HT3A receptor expressed in mammalian cells. Selectivity refers to the 5-HT3 receptor family: the agents listed no not discriminate between 5-HT3A and 5-HT3AB receptors in radioligand binding assays. In electrophysiological studies, (+)-tubocurarine demonstrates modest selectivity for human 5-HT3A (IC50 = 3 μM) versus human 5-HT3AB (IC50 = 14 – 21 μM) receptors [12]. Where significant species differences in antagonist affinity exist, data for the mouse orthologue of the receptor are also listed.
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
TMB-8 Small molecule or natural product Mm - no 5.1 – 5.3 pIC50 - no 35,51
⤷ pIC50 5.1 – 5.3 (IC50 8.4x10-6 – 4.5x10-6 M) [35,51]
Not voltage dependent
picrotoxinin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - no 5.0 pIC50 - no 52
⤷ pIC50 5.0 (IC50 1.1x10-5 M) [52]
Not voltage dependent
TMB-8 Small molecule or natural product Hs - no 4.9 pIC50 - no 51
⤷ pIC50 4.9 (IC50 1.176x10-5 M) [51]
Not voltage dependent
diltiazem Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Mm - yes 4.2 – 5.3 pIC50 - yes (-60.0) 18,35
⤷ pIC50 4.2 – 5.3 (IC50 7.14x10-5 – 5.5x10-6 M) [18,35]
Voltage dependent: -60.0 mV
diltiazem Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - no 4.7 pIC50 - no 52
⤷ pIC50 4.7 (IC50 2.1x10-5 M) [52]
Not voltage dependent
picrotoxin Small molecule or natural product Click here for species-specific activity table Mm - yes 4.4 – 4.5 pIC50 - no 9-10
⤷ pIC50 4.4 – 4.5 [9-10]
Not voltage dependent
bilobalide Small molecule or natural product Click here for species-specific activity table Hs - no 3.3 pIC50 - no 52
⤷ pIC50 3.3 (IC50 4.7x10-4 M) [52]
Not voltage dependent
ginkgolide B Small molecule or natural product Click here for species-specific activity table Hs - no 3.1 pIC50 - no 52
⤷ pIC50 3.1 (IC50 7.3x10-4 M) [52]
Not voltage dependent
View species-specific channel blocker tables
Channel Blocker Comments
Although picrotoxin is approximately 27-fold more potent in blocking mouse 5-HT3A versus mouse 5-HT3AB receptors, the degree of discrimination between the equivalent human receptor orthologues is likely to be substantially smaller due to differences in the structure of the TM2 domain [11].
Allosteric Modulators
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
ethanol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Positive - - 3x10-2 - 3x10-1 no 13,22,25,56
⤷ Conc range: 3x10-2 - 3x10-1 M increased channel activation rate, decreased desensitisation rate, decreased deactivation rate. [13,22,25,56]
Not voltage dependent
Mg2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Negative - - 1x10-3 - 1x10-2 no 41
⤷ Conc range: 1x10-3 - 1x10-2 M Decrease in agonist apparent affinity. [41]
Not voltage dependent
Mg2+ Click here for species-specific activity table Ligand is endogenous in the given species Mm Negative - - 1x10-3 - 1x10-2 no 17,44
⤷ Conc range: 1x10-3 - 1x10-2 M decrease in agonist apparent affinity. [17,44]
Not voltage dependent
5-hydroxyindole Small molecule or natural product Ligand has a PDB structure Mm Positive - - 1x10-3 - 1x10-2 no 18,28,33,53
⤷ Conc range: 1x10-3 - 1x10-2 M decreased desensitization rate, decreased deactivation rate, increased apparent affinty of 5-HT. [18,28,33,53]
Not voltage dependent
trichloroethanol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Positive - - 2.5x10-4 - 1x10-2 no 13,22,25,27,56
⤷ Conc range: 2.5x10-4 - 1x10-2 M increased channel activation rate, decreased desensitization rate, decreased deactivation rate. [13,22,25,27,56]
Not voltage dependent
Ca2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Negative - - 1x10-4 - 1x10-2 no 6,41
⤷ Conc range: 1x10-4 - 1x10-2 M Decreased single channel conductance, increased channel activation rate, increased deactivation rate, increased desensitization rate, decrease in agonist apparent affinity. [6,41]
Not voltage dependent
Ca2+ Click here for species-specific activity table Ligand is endogenous in the given species Mm Negative - - 1x10-4 - 1x10-2 no 17,26,44
⤷ Conc range: 1x10-4 - 1x10-2 M Decreased single channel conductance, increased channel activation rate, increased deactivation rate, increased desensitization rate, decrease in agonist apparent affinity. [17,26,44]
Not voltage dependent
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Mm Biphasic - - 1x10-6 - 3x10-4 no 17,29
⤷ Conc range: 1x10-6 - 3x10-4 M Positive (1-10μM): increased potency of 5-HT, decreased desensitization rate, reduced effect in the presence of Mg2+ or Ca2+. Negative (30-300μM). [17,29]
Not voltage dependent
View species-specific allosteric modulator tables
Allosteric Modulator Comments
Numerous positive modulators of the 5-HT3A receptor exist, but most also exert effects at other ligand-gated ion channels. Only the most extensively characterised are listed above together with an indication of the range of concentrations over which they modulate submaximal inward currents evoked by 5-HT acting on either mouse of human 5-HT3A receptors expressed in Xenopus laevis oocytes or HEK-293 cells, or 5-HT3 receptors endogenous to clonal cell lines (which are likely to be homomeric 5-HT3A receptors). Chloroform, halothane and small volume n-alcohols enhance the gating of 5-HT3A receptors and incorporation of the 5-HT3B subunit to form 5-HT3AB receptors suppresses this action [49-50].
Functional Assays Click here for help
Measurement of cation current in Xenopus oocytes expressing the 5-HT3A subunit.
Species:  Human
Tissue:  Xenopus laevis oocytes
Response measured:  Cation current under voltage-clamp.
References:  3,39
Measurement of cation current in HEK-293 cells transfected with the 5-HT3A subunit.
Species:  Human
Tissue:  HEK-293 cells
Response measured:  Cation current under voltage-clamp.
References:  6,19,32,41
Measurement of intracellular Ca2+ increase using a FlexStation in HEK-293 cells transfected with the 5-HT3A subunit.
Species:  Mouse
Tissue:  HEK-293 cells
Response measured:  Ca2+-sensitive change in fluorescence.
References:  47
Measurement of [14C]-guanidinium influx in HEK-293 cells transfected with the 5-HT3A subunit.
Species:  Mouse
Tissue:  HEK-293 cells
Response measured:  Intracellular accumulation of ratiotracer.
References:  7
Measurement of intracellular Ca2+ increase using single cell video imaging in HEK-293 cells transfected with the 5-HT3A subunit.
Species:  Mouse
Tissue:  HEK-293 cells
Response measured:  Ca2+-sensitive change in fluorescence.
References:  20
Measurement of Ca2+-induced aequorin luminescence in HEK-293 cells co-transfected with the 5-HT3A subunit and aequorin.
Species:  Human
Tissue:  HEK-293 cells
Response measured:  Ca2+-sensitive change in fluorescence.
References:  54
Indirect measurement of membrane potential using a FlexStation with HEK-293 cells transfected with the 5-HT3A subunit.
Species:  Mouse
Tissue:  HEK-293 cells
Response measured:  Voltage-sensitive change in fluorescence
References:  47

References

Show »

1. Abi-Dargham A, Laruelle M, Wong DT, Robertson DW, Weinberger DR, Kleinman JE. (1993) Pharmacological and regional characterization of [3H]LY278584 binding sites in human brain. J Neurochem, 60 (2): 730-7. [PMID:8419547]

2. Bang-Andersen B, Ruhland T, Jørgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mørk A et al.. (2011) Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem, 54 (9): 3206-21. [PMID:21486038]

3. Belelli D, Balcarek JM, Hope AG, Peters JA, Lambert JJ, Blackburn TP. (1995) Cloning and functional expression of a human 5-hydroxytryptamine type 3AS receptor subunit. Mol Pharmacol, 48 (6): 1054-62. [PMID:8848005]

4. Bonhaus DW, Stefanich E, Loury DN, Hsu SA, Eglen RM, Wong EH. (1995) Allosteric interactions among agonists and antagonists at 5-hydroxytryptamine3 receptors. J Neurochem, 65 (1): 104-10. [PMID:7790853]

5. Brady CA, Stanford IM, Ali I, Lin L, Williams JM, Dubin AE, Hope AG, Barnes NM. (2001) Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors. Neuropharmacology, 41 (2): 282-4. [PMID:11489465]

6. Brown AM, Hope AG, Lambert JJ, Peters JA. (1998) Ion permeation and conduction in a human recombinant 5-HT3 receptor subunit (h5-HT3A). J Physiol (Lond.), 507 ( Pt 3): 653-65. [PMID:9508827]

7. Brüss M, Molderings GJ, Bönisch H, Göthert M. (1999) Pharmacological differences and similarities between the native mouse 5-HT3 receptor in N1E-115 cells and a cloned short splice variant of the mouse 5-HT3 receptor expressed in HEK 293 cells. Naunyn Schmiedebergs Arch Pharmacol, 360 (3): 225-33. [PMID:10543422]

8. Dang H, England PM, Farivar SS, Dougherty DA, Lester HA. (2000) Probing the role of a conserved M1 proline residue in 5-hydroxytryptamine(3) receptor gating. Mol Pharmacol, 57 (6): 1114-22. [PMID:10825381]

9. Das P, Bell-Horner CL, Machu TK, Dillon GH. (2003) The GABA(A) receptor antagonist picrotoxin inhibits 5-hydroxytryptamine type 3A receptors. Neuropharmacology, 44 (4): 431-8. [PMID:12646280]

10. Das P, Dillon GH. (2003) The 5-HT3B subunit confers reduced sensitivity to picrotoxin when co-expressed with the 5-HT3A receptor. Brain Res Mol Brain Res, 119 (2): 207-12. [PMID:14625088]

11. Das P, Dillon GH. (2005) Molecular determinants of picrotoxin inhibition of 5-hydroxytryptamine type 3 receptors. J Pharmacol Exp Ther, 314 (1): 320-8. [PMID:15814570]

12. Davies PA, Pistis M, Hanna MC, Peters JA, Lambert JJ, Hales TG, Kirkness EF. (1999) The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature, 397 (6717): 359-63. [PMID:9950429]

13. Downie DL, Hope AG, Belelli D, Lambert JJ, Peters JA, Bentley KR, Steward LJ, Chen CY, Barnes NM. (1995) The interaction of trichloroethanol with murine recombinant 5-HT3 receptors. Br J Pharmacol, 114 (8): 1641-51. [PMID:7541281]

14. Downie DL, Hope AG, Lambert JJ, Peters JA, Blackburn TP, Jones BJ. (1994) Pharmacological characterization of the apparent splice variants of the murine 5-HT3 R-A subunit expressed in Xenopus laevis oocytes. Neuropharmacology, 33 (3-4): 473-82. [PMID:7984286]

15. Dubin AE, Huvar R, D'Andrea MR, Pyati J, Zhu JY, Joy KC, Wilson SJ, Galindo JE, Glass CA, Luo L et al.. (1999) The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit. J Biol Chem, 274 (43): 30799-810. [PMID:10521471]

16. Edwards E, Hampton E, Ashby CR, Zhang J, Wang RY. (1996) 5-HT3-like receptors in the rat medial prefrontal cortex: further pharmacological characterization. Brain Res, 733 (1): 21-30. [PMID:8891244]

17. Gill CH, Peters JA, Lambert JJ. (1995) An electrophysiological investigation of the properties of a murine recombinant 5-HT3 receptor stably expressed in HEK 293 cells. Br J Pharmacol, 114 (6): 1211-21. [PMID:7620711]

18. Gunthorpe MJ, Lummis SC. (1999) Diltiazem causes open channel block of recombinant 5-HT3 receptors. J Physiol (Lond.), 519 Pt 3: 713-22. [PMID:10457085]

19. Hales TG, Dunlop JI, Deeb TZ, Carland JE, Kelley SP, Lambert JJ, Peters JA. (2006) Common determinants of single channel conductance within the large cytoplasmic loop of 5-hydroxytryptamine type 3 and alpha4beta2 nicotinic acetylcholine receptors. J Biol Chem, 281 (12): 8062-71. [PMID:16407231]

20. Hargreaves AC, Lummis SC, Taylor CW. (1994) Ca2+ permeability of cloned and native 5-hydroxytryptamine type 3 receptors. Mol Pharmacol, 46 (6): 1120-8. [PMID:7808432]

21. Hassaine G, Deluz C, Grasso L, Wyss R, Tol MB, Hovius R, Graff A, Stahlberg H, Tomizaki T, Desmyter A et al.. (2014) X-ray structure of the mouse serotonin 5-HT3 receptor. Nature, 512 (7514): 276-81. [PMID:25119048]

22. Hayrapetyan V, Jenschke M, Dillon GH, Machu TK. (2005) Co-expression of the 5-HT(3B) subunit with the 5-HT(3A) receptor reduces alcohol sensitivity. Brain Res Mol Brain Res, 142 (2): 146-50. [PMID:16257471]

23. Hirata T, Keto Y, Funatsu T, Akuzawa S, Sasamata M. (2007) Evaluation of the pharmacological profile of ramosetron, a novel therapeutic agent for irritable bowel syndrome. J Pharmacol Sci, 104 (3): 263-73. [PMID:17652911]

24. Hope AG, Peters JA, Brown AM, Lambert JJ, Blackburn TP. (1996) Characterization of a human 5-hydroxytryptamine3 receptor type A (h5-HT3R-AS) subunit stably expressed in HEK 293 cells. Br J Pharmacol, 118 (5): 1237-45. [PMID:8818349]

25. Hu XQ, Hayrapetyan V, Gadhiya JJ, Rhubottom HE, Lovinger DM, Machu TK. (2006) Mutations of L293 in transmembrane two of the mouse 5-hydroxytryptamine3A receptor alter gating and alcohol modulatory actions. Br J Pharmacol, 148 (1): 88-101. [PMID:16520747]

26. Hu XQ, Lovinger DM. (2005) Role of aspartate 298 in mouse 5-HT3A receptor gating and modulation by extracellular Ca2+. J Physiol (Lond.), 568 (Pt 2): 381-96. [PMID:16096341]

27. Hu XQ, Peoples RW. (2008) Arginine 246 of the pretransmembrane domain 1 region alters 2,2,2-trichloroethanol action in the 5-hydroxytryptamine3A receptor. J Pharmacol Exp Ther, 324 (3): 1011-8. [PMID:18094321]

28. Hu XQ, Peoples RW. (2008) The 5-HT3B subunit confers spontaneous channel opening and altered ligand properties of the 5-HT3 receptor. J Biol Chem, 283 (11): 6826-31. [PMID:18187416]

29. Hubbard PC, Lummis SC. (2000) Zn(2+) enhancement of the recombinant 5-HT(3) receptor is modulated by divalent cations. Eur J Pharmacol, 394 (2-3): 189-97. [PMID:10771284]

30. Hussy N, Lukas W, Jones KA. (1994) Functional properties of a cloned 5-hydroxytryptamine ionotropic receptor subunit: comparison with native mouse receptors. J Physiol (Lond.), 481 ( Pt 2): 311-23. [PMID:7537814]

31. Ito H, Kiso T, Miyata K, Kamato T, Yuki H, Akuzawa S, Nagakura Y, Yamano M, Suzuki M, Naitoh Y et al.. (2000) Pharmacological profile of YM-31636, a novel 5-HT3 receptor agonist, in vitro. Eur J Pharmacol, 409 (2): 195-201. [PMID:11104834]

32. Kelley SP, Dunlop JI, Kirkness EF, Lambert JJ, Peters JA. (2003) A cytoplasmic region determines single-channel conductance in 5-HT3 receptors. Nature, 424 (6946): 321-4. [PMID:12867984]

33. Kooyman AR, van Hooft JA, Vijverberg HP. (1993) 5-Hydroxyindole slows desensitization of the 5-HT3 receptor-mediated ion current in N1E-115 neuroblastoma cells. Br J Pharmacol, 108 (2): 287-9. [PMID:7680589]

34. Lankiewicz S, Lobitz N, Wetzel CH, Rupprecht R, Gisselmann G, Hatt H. (1998) Molecular cloning, functional expression, and pharmacological characterization of 5-hydroxytryptamine3 receptor cDNA and its splice variants from guinea pig. Mol Pharmacol, 53 (2): 202-12. [PMID:9463477]

35. Lee BH, Choi SH, Pyo MK, Shin TJ, Hwang SH, Kim BR, Lee JH, Rhim H, Kim HC, Nah SY. (2009) A role for the Val291 residue within the transmembrane domain 2 in diltiazem- and TMB-8 [3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester]-mediated 5-hydroxytryptamine type 3A receptor regulations. Biol Pharm Bull, 32 (5): 861-7. [PMID:19420755]

36. Livesey MR, Cooper MA, Deeb TZ, Carland JE, Kozuska J, Hales TG, Lambert JJ, Peters JA. (2008) Structural determinants of Ca2+ permeability and conduction in the human 5-hydroxytryptamine type 3A receptor. J Biol Chem, 283 (28): 19301-13. [PMID:18474595]

37. Mair ID, Lambert JJ, Yang J, Dempster J, Peters JA. (1998) Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT3A(b)) expressed in Xenopus laevis oocytes. Br J Pharmacol, 124 (8): 1667-74. [PMID:9756382]

38. Mazurov AA, Speake JD, Yohannes D. (2011) Discovery and development of α7 nicotinic acetylcholine receptor modulators. J Med Chem, 54 (23): 7943-61. [PMID:21919481]

39. Miyake A, Mochizuki S, Takemoto Y, Akuzawa S. (1995) Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species. Mol Pharmacol, 48 (3): 407-16. [PMID:7565620]

40. Mochizuki S, Miyake A, Furuichi K. (1999) Identification of a domain affecting agonist potency of meta-chlorophenylbiguanide in 5-HT3 receptors. Eur J Pharmacol, 369 (1): 125-32. [PMID:10204690]

41. Mochizuki S, Miyake A, Furuichi K. (1999) Ion permeation properties of a cloned human 5-HT3 receptor transiently expressed in HEK 293 cells. Amino Acids, 17 (3): 243-55. [PMID:10582123]

42. Moura Barbosa AJ, De Rienzo F, Ramos MJ, Menziani MC. (2010) Computational analysis of ligand recognition sites of homo- and heteropentameric 5-HT3 receptors. Eur J Med Chem, 45 (11): 4746-60. [PMID:20724042]

43. Niemeyer MI, Lummis SC. (1998) Different efficacy of specific agonists at 5-HT3 receptor splice variants: the role of the extra six amino acid segment. Br J Pharmacol, 123 (4): 661-6. [PMID:9517385]

44. Niemeyer MI, Lummis SC. (2001) The role of the agonist binding site in Ca(2+) inhibition of the recombinant 5-HT(3A) receptor. Eur J Pharmacol, 428 (2): 153-61. [PMID:11675031]

45. Noam Y, Wadman WJ, van Hooft JA. (2008) On the voltage-dependent Ca2+ block of serotonin 5-HT3 receptors: a critical role of intracellular phosphates. J Physiol (Lond.), 586 (15): 3629-38. [PMID:18566001]

46. Parker RM, Barnes JM, Ge J, Barber PC, Barnes NM. (1996) Autoradiographic distribution of [3H]-(S)-zacopride-labelled 5-HT3 receptors in human brain. J Neurol Sci, 144 (1-2): 119-27. [PMID:8994113]

47. Price KL, Lummis SC. (2005) FlexStation examination of 5-HT3 receptor function using Ca2+ - and membrane potential-sensitive dyes: advantages and potential problems. J Neurosci Methods, 149 (2): 172-7. [PMID:16038983]

48. Roberts A, Grafton G, Powell AD, Brock K, Chen C, Xie D, Huang J, Liu S, Cooper AJ, Brady CA et al.. (2020) CSTI-300 (SMP-100); a Novel 5-HT3 Receptor Partial Agonist with Potential to Treat Patients with Irritable Bowel Syndrome or Carcinoid Syndrome. J Pharmacol Exp Ther, 373 (1): 122-134. [PMID:32102919]

49. Rüsch D, Musset B, Wulf H, Schuster A, Raines DE. (2007) Subunit-dependent modulation of the 5-hydroxytryptamine type 3 receptor open-close equilibrium by n-alcohols. J Pharmacol Exp Ther, 321 (3): 1069-74. [PMID:17360702]

50. Solt K, Stevens RJ, Davies PA, Raines DE. (2005) General anesthetic-induced channel gating enhancement of 5-hydroxytryptamine type 3 receptors depends on receptor subunit composition. J Pharmacol Exp Ther, 315 (2): 771-6. [PMID:16081679]

51. Sun H, McCardy EA, Machu TK, Blanton MP. (1999) Characterization of interaction of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester with Torpedo californica nicotinic acetylcholine receptor and 5-hydroxytryptamine3 receptor. J Pharmacol Exp Ther, 290 (1): 129-35. [PMID:10381768]

52. Thompson AJ, Duke RK, Lummis SC. (2011) Binding sites for bilobalide, diltiazem, ginkgolide, and picrotoxinin at the 5-HT3 receptor. Mol Pharmacol, 80 (1): 183-90. [PMID:21505038]

53. van Hooft JA, van der Haar E, Vijverberg HP. (1997) Allosteric potentiation of the 5-HT3 receptor-mediated ion current in N1E-115 neuroblastoma cells by 5-hydroxyindole and analogues. Neuropharmacology, 36 (4-5): 649-53. [PMID:9225290]

54. Walstab J, Combrink S, Brüss M, Göthert M, Niesler B, Bönisch H. (2007) Aequorin luminescence-based assay for 5-hydroxytryptamine (serotonin) type 3 receptor characterization. Anal Biochem, 368 (2): 185-92. [PMID:17617370]

55. Yan D, Pedersen SE, White MM. (1998) Interaction of D-tubocurarine analogs with the 5HT3 receptor. Neuropharmacology, 37 (2): 251-7. [PMID:9680250]

56. Zhou Q, Verdoorn TA, Lovinger DM. (1998) Alcohols potentiate the function of 5-HT3 receptor-channels on NCB-20 neuroblastoma cells by favouring and stabilizing the open channel state. J Physiol (Lond.), 507 ( Pt 2): 335-52. [PMID:9518697]

Contributors

Show »

How to cite this page