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5-HT1A

Structural Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Name Reference
Human 7 422 5q11.2-q13 HTR1A 3-4
Rat 7 422 2q16 Htr1a 1-2
Mouse 7 421 13 D2.1 Htr1a 5
Contents:
Structural Information
Database Links
Agonists
Antagonists
Allosteric Regulators
Transduction Mechanisms
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Biologically Significant Variants
Database Links
ChEMBL Target 51 (Hs), 11863 (Mm), 10576 (Rn)
Ensembl ENSG00000178394 (Hs), ENSMUSG00000021721 (Mm), ENSRNOG00000010254 (Rn)
Entrez Gene 3350 (Hs), 15550 (Mm), 24473 (Rn)
GeneCards HTR1A (Hs)
HomoloGene 20148 (Hs)
OMIM 109760 (Hs)
PharmGKB Gene PA192 (Hs)
Protein Ontology (PRO) PRO:000001161 (Hs)
RefSeq Nucleotide NM_000524 (Hs), NM_008308 (Mm), NM_012585 (Rn)
RefSeq Protein NP_000515 (Hs), NP_032334 (Mm), NP_036717 (Rn)
UniGene Hs. 247940 (Hs)
UniProt P08908 (Hs), Q64264 (Mm), P19327 (Rn)
Wikipedia 5-HT1A
Search for 3D structures on the PDB
Search using keywords: 5-Hydroxytryptamine receptors 5-HT1A Search using accession numbers: P19327 || P08908 || Q64264
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]8-OH-DPAT Hs Full agonist 6.0 – 9.4 pKd 48,50,52,62
[3H]S-15535 Hs Partial agonist 5.8 – 5.9 pKd 50
S-14671 Hs Full agonist 10.2 – 10.5 pKi 47,50
LY293284 Hs Full agonist 10.1 pKi 62
5-CT Hs Full agonist 9.4 – 10.3 pKi 21,47,50-51
lisuride Hs Full agonist 9.7 – 9.8 pKi 50-51,69
U92012A Hs Full agonist 9.7 pKi 68
roxindole Hs Partial agonist 9.4 – 9.9 pKi 48,69
S-14506 Hs Full agonist 9.6 – 9.7 pKi 47,50
5-HT Hs Full agonist 9.1 – 9.7 pKi 21,47-48,50-52
(+)-flesinoxan Hs Full agonist 9.3 pKi 47
L-694,247 Hs Full agonist 9.3 pKi 51
S-15535 Hs Partial agonist 9.2 pKi 50
LSD Hs Full agonist 9.0 pKi 61
RU 24969 Hs Full agonist 9.0 pKi 47
8-OH-DPAT Hs Full agonist 8.4 – 9.4 pKi 21,47,50,52-56
LY 165,163 Hs Full agonist 8.9 pKi 47
spiroxatrine Hs Full agonist 8.8 pKi 47
ipsapirone Hs Partial agonist 8.6 – 8.8 pKi 47,50
FG-5893 Hs Full agonist 8.7 pKi 47
pergolide Hs Partial agonist 8.7 pKi 69
7-methoxy-1-naphthylpiperazine Hs Full agonist 8.6 pKi 49
terguride Hs Partial agonist 8.5 pKi 69
S 16924 Hs Partial agonist 8.4 pKi 66
ziprasidone Hs Partial agonist 7.9 – 8.9 pKi 47,65
aripiprazole Hs Full agonist 8.2 pKi 70
tandospirone Hs Full agonist 8.2 pKi 47
ORG-5222 Hs Full agonist 8.0 – 8.3 pKi 47,65
zalospirone Hs Full agonist 8.1 pKi 47
1-naphthylpiperazine Hs Full agonist 8.0 pKi 49
ocaperidone Hs Full agonist 8.0 pKi 22
bromocriptine Hs Partial agonist 7.9 pKi 69
buspirone Hs Partial agonist 7.7 – 8.0 pKi 21,47,50
LY334370 Hs Full agonist 7.8 pKi 63
BRL-15572 Hs Partial agonist 7.7 pKi 58
cabergoline Hs Full agonist 7.7 pKi 69
donitriptan Hs Full agonist 7.6 pKi 71
eletriptan Hs Full agonist 7.4 pKi 72
naratriptan Hs Full agonist 7.1 – 7.6 pKi 51,72
nafadotride Hs Full agonist 7.3 pKi 47
BMY-14802 Hs Full agonist 7.2 pKi 47
xanomeline Hs Full agonist 7.2 pKi 73
GR-127935 Hs Partial agonist 7.1 – 7.2 pKi 49,58
apomorphine Hs Partial agonist 6.9 pKi 69
clozapine Hs Full agonist 6.8 – 6.9 pKi 47,65-66
EMDT Hs Full agonist 6.8 pKi 59
fluparoxan Hs Partial agonist 6.8 pKi 54
zolmitriptan Hs Full agonist 6.6 pKi 72
quetiapine Hs Full agonist 6.5 – 6.6 pKi 47,65
piribedil Hs Partial agonist 6.4 pKi 69
rizatriptan Hs Full agonist 6.4 pKi 72
LY344864 Hs Full agonist 6.3 pKi 64
SB 216641 Hs Partial agonist 6.3 pKi 58
CP 93129 Hs Full agonist 6.1 pKi 51
SL65.0155 Hs Partial agonist 6.0 pKi 67
sumatriptan Hs Full agonist 6.0 pKi 72
(-)-quinpirole Hs Full agonist 5.8 pKi 48
olanzapine Hs Full agonist 5.6 – 5.8 pKi 47,65
BMY-7378 Hs Partial agonist 6.8 – 8.0 pIC50 57
L-772,405 Hs Full agonist 7.2 pIC50 60
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]NAD 299 Hs Antagonist 9.8 pKd 80
[3H]-p-MPPF Hs Antagonist 8.4 pKd 52
Rec 15/3079 Hs Antagonist 9.7 pKi 77
NAN 190 Hs Antagonist 9.4 pKi 47
repinotan Hs Antagonist 9.4 pKi 53
NAD 299 Hs Antagonist 9.2 pKi 76
SB 649915 Hs Antagonist 8.6 pKi 79
WAY-100635 Hs Antagonist 7.9 – 9.2 pKi 47,50
p-MPPI Hs Antagonist 8.4 pKi 52
tiospirone Hs Antagonist 8.3 pKi 47
(+)-UH 301 Hs Antagonist 7.9 – 8.6 pKi 47
(-)-tertatolol Hs Antagonist 8.2 pKi 47,56
pindolol Hs Antagonist 8.1 pKi 50
SB 272183 Hs Antagonist 8.0 pKi 78
WAY-100135 Hs Antagonist 8.0 pKi 50
methiothepin Hs Antagonist 7.8 – 8.1 pKi 47,50
spiperone Hs Antagonist 6.7 – 8.8 pKi 21,47,50
(-)-propranolol Hs Antagonist 7.5 pKi 51
(S)-flurocarazolol Hs Antagonist 7.5 pKi 74
pizotifen Hs Antagonist 7.4 pKi 51
GR 125,743 Hs Antagonist 7.3 pKi 51
yohimbine Hs Antagonist 7.3 pKi 54
fluspirilene Hs Antagonist 7.2 pKi 65
thioridazine Hs Antagonist 7.1 pKi 47
iloperidone Hs Antagonist 7.0 pKi 82
GR 218,231 Hs Antagonist 6.8 pKi 75
iloperidone Rn Antagonist 6.8 pKi 81
pimozide Hs Antagonist 6.8 pKi 47
(R)-flurocarazolol Hs Antagonist 6.5 pKi 74
SB 714786 Hs Antagonist 6.5 pKi 79
sertindole Hs Antagonist 6.4 – 6.6 pKi 47,65
zotepine Hs Antagonist 6.5 pKi 65
risperidone Hs Antagonist 6.4 – 6.5 pKi 47,65
(+)-butaclamol Hs Antagonist 6.4 pKi 47
cyamemazine Hs Antagonist 6.3 pKi 55
9-OH-risperidone Hs Antagonist 6.2 pKi 65
chlorpromazine Hs Antagonist 6.2 pKi 47
risperidone Rn Antagonist 6.2 pKi 81
MPDT Hs Antagonist 5.8 pKi 59
haloperidol Hs Antagonist 5.7 – 5.8 pKi 47,56,65-66
pipamperone Hs Antagonist 5.6 pKi 65
raclopride Hs Antagonist 5.2 pKi 47
ketanserin Hs Antagonist 5.0 pKi 21
SDZ-216525 Hs Antagonist 7.8 – 8.2 pIC50 57
ritanserin Hs Antagonist 5.2 – 5.5 pIC50 57
View species-specific antagonist tables
Allosteric Regulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
RS-30199 Hs Positive 7.1 – 7.6 pKi 83

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Comments:  The 5-HT1A has also been found to stimulate cAMP accumulation via Gi2 and ACII [6].
References:  3,6-7
Secondary Transduction Mechanisms
Transducer Effector/Response
Phospholipase C stimulation
References:  3
Tissue Distribution
Limbic system: septum, hippocampus, thalamus, amygdala, olfactory bulb, medulla, mesencephalon, hypothalamus.
Species:  Rat
Technique:  Northern blotting.
References:  2
Kidney: medullary and cortical thick ascending limbs (TAL), distal convoluted tubules (DCT), connecting tubule cells, principal cells of the initial collecting tubule.
Species:  Rat
Technique:  Immunohistochemistry.
References:  24
Benign and malignant prostate tissue.
Species:  Human
Technique:  Western blotting.
References:  25
Posterior taste buds.
Species:  Rat
Technique:  RT-PCR.
References:  26
Peritoneal macrophages.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  27
Brain: pyramidal and principal cells and calbindin- and parvalbumin-containing neurons.
Species:  Rat
Technique:  Immunohistochemistry.
References:  28
Poorly expressed in coronary arteries, atrium, ventricle and epicardium.
Species:  Human
Technique:  RT-PCR.
References:  29
Spinal cord: dorsal horn > ventral horn.
Species:  Human
Technique:  Radioligand binding.
References:  30
CNS: dentate gyrus, hippocampus (all fields especially CA1), subiculum, parahippocampal gyrus and neocortical regions (superficial and middle laminae), raphe of the brainstem.
Species:  Human
Technique:  in situ hybridisation.
References:  31
CNS: Dorsal raphe nucleus, septum, hippocampus, entorhinal cortex, interpeduncular nucleus > olfactory bulb, cerebral cortex, thalamic and hypothalamic nuclei, nuclei of the brainstem, dorsal horn of the spinal cord.
Species:  Rat
Technique:  in situ hybridisation.
References:  32
Superior cervical ganglia, lumbar sympathetic ganglia.
Species:  Rat
Technique:  RT-PCR.
References:  33
Kidney: medullary and cortical thick ascending limbs (TAL), distal convoluted tubules (DCT), connecting tubule cells, principal cells of the initial collecting tubule.
Species:  Human
Technique:  Immunohistochemistry.
References:  24
Functional Assays
Measurement of cAMP levels in COS-7 cells transfected with the 5-HT1A receptor.
Species:  Human
Tissue:  COS-7
Response measured:  Inhibition of cAMP accumulation.
References:  3,21
Measurement of IP3 levels in HeLa cells transfected with the 5-HT1A receptor.
Species:  Human
Tissue:  HeLa cells.
Response measured:  PLC mediated IP3 accumulation.
References:  3
Measurement of cAMP levels in rat CH4ZD10 cells endogenously expressing the 5-HT1A receptor.
Species:  Rat
Tissue:  CH4ZD10 cells.
Response measured:  PTX-sensitive inhibition of cAMP accumulation.
References:  2
Measurement of cAMP levels in SN-48 cells endogenously expressing the 5-HT1A receptor.
Species:  Mouse
Tissue:  Differentiated SN-48 cell line.
Response measured:  Inhibition of cAMP accumulation.
References:  5
Measurement of cAMP levels in HEK 293 cells transfected with the rat 5-HT1A receptor alone/with adenylyl cyclase II (ACII).
Species:  Rat
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation in the absence of ACII.
Increase in cAMP accumulation in the presence of ACII.
References:  6
Measurement of extracellular acidification rate (ECAR) in CHO-K1 cells transfected with the 5-HT1A receptor.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Activation of the Na+/H+ exchanger.
References:  22
Measurement of phosphorylated ERK1/2 levels in the rat hippocampus.
Species:  Rat
Tissue:  Hippocampus.
Response measured:  Inhibition of the Erk1/2 MAPK pathway.
References:  23
Physiological Functions
Stimulation of cell proliferation.
Species:  Human
Tissue:  DU145, PC-3, LNCaP and hPCP prostatic cell lines.
References:  25
Increase in phagocytic activity.
Species:  Mouse
Tissue:  Peritoneal macrophages.
References:  27
Hyperpolarisation of orexin neurons.
Species:  Mouse
Tissue:  Hypothalamus.
References:  34
Regulation of sleep-wakefulness cycles.
Species:  Rat
Tissue:  In vivo.
References:  35-36
Regulation of sleep-wakefulness cycles.
Species:  Mouse
Tissue:  In vivo.
References:  8
Regulation of epileptic activity.
Species:  Rat
Tissue:  In vivo.
References:  37
Regulation of oxytocin and adrenocorticotropin hormone release.
Species:  Rat
Tissue:  In vivo (paraventricular nucleus).
References:  38
Adult brain cell proliferation.
Species:  Rat
Tissue:  Subgranular layer (SGL) of the dentate gyrus (DG) and the subventricular zone (SVZ).
References:  39
Autoreceptor: autoinhibitory control.
Species:  Mouse
Tissue:  In vivo (dorsal raphe nucleus).
References:  9
Regulation of cholinergic, GABAergic and glutamatergic transmission and hence cognitive performance.
Species:  Mouse
Tissue:  In vivo.
References:  40
Regulation of anxiety-like behaviour.
Species:  Mouse
Tissue:  In vivo.
References:  10
Regulation of stress responses and locomotor activity.
Species:  Mouse
Tissue:  In vivo (hypothalamus).
References:  41
Regulation of aggressive bahaviour.
Species:  Rat
Tissue:  In vivo.
References:  42
Regulation of feeding behaviour by inducing preproNPY mRNA expression.
Species:  Rat
Tissue:  In vivo (arcuate nucleus).
References:  43
Facilitation of autoshaped learning.
Species:  Mouse
Tissue:  In vivo.
References:  17
Regulation of hippocampal functions.
Species:  Rat
Tissue:  In vivo.
References:  44
Antinociception.
Species:  Rat
Tissue:  In vivo.
References:  45-46
Physiological Consequences of Altering Gene Expression
5-HT1A receptor knockout mice exhibit higher amounts of paradoxical sleep than wild-type mice during both the light and the dark phases.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  8
5-HT1A receptor knockout mice have an increased responsiveness to 5-HT in the dorsal raphe nucleus due to lack of autoinhibitory control by 5-HT1A autoreceptors.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  9
Increased 5-HT1A receptor expression during postnatal development caused elevated 5-HT levels in the hippocampus and striatum, decreased anxiety-like behaviour (in male and female) and decreased body temperature (male only).
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  10
Temporary 5-HT1A receptor overexpression during embryonic and perinatal development causes long-term memory impairment.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  11
5-HT1A receptor knockout mice show increases in typical anxiety and stress responses.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  12-14
5-HT1A receptor knockout mice exhibit down-regulation of the 5-HT transporter.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  15
5-HT1A receptor knockout mice exhibit a deficit in hippocampal-dependent learning and memory as well as higher limbic excitability.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  16
5-HT1A receptor knockout mice exhibit altered decision making abilities and response inhibition.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  17
Biologically Significant Variants
Two polymorphisms, Gly22 -> Ser and Ile28 -> Val, have been found to alter the extracellular amino terminal region of the receptor.
Type:  Single nucletide polymorphisms.
Species:  Human
References:  18
The polymorphism Arg219 -> Leu has been associated with Tourette's syndrome.
Type:  Single nucleotide polymorphism.
Species:  Human
References:  19
The polymorphism Ala50 -> Val, occurring in transmembrane 1, results in a loss of response to 5-HT.
Type:  Single nucleotide polymorphism.
Species:  Human
References:  20

To cite this receptor data page, please use the following:

Rodrigo Andrade, Nicholas M. Barnes, Gordon Baxter, Joel Bockaert, Theresa Branchek, Marlene L. Cohen, Aline Dumuis, Richard M. Eglen, Manfred Göthert, Mark Hamblin, Michel Hamon, Paul R. Hartig, René Hen, Katharine Herrick-Davis, Rebecca Hills, Daniel Hoyer, Patrick P. A. Humphrey, Klaus Peter Latté, Luc Maroteaux, Graeme R. Martin, Derek N. Middlemiss, Ewan Mylecharane, Stephen J. Peroutka, Pramod R. Saxena, Andrew Sleight, Carlos M. Villalon, Frank Yocca.
5-Hydroxytryptamine receptors: 5-HT1A. Last modified on 2010-08-03. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=1.


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