Affinage

HTR1A

5-hydroxytryptamine receptor 1A · UniProt P08908

Round 2 corrected
Length
422 aa
Mass
46.1 kDa
Annotated
2026-04-28
130 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HTR1A encodes the 5-hydroxytryptamine receptor 1A, a Gi/o-coupled GPCR that inhibits adenylyl cyclase at nanomolar serotonin concentrations and activates phospholipase C at higher agonist occupancy, both via pertussis toxin-sensitive G proteins, with cell-type-dependent preferential coupling to Gαi2 or Gαi3 (PMID:2549039, PMID:8218170). As a somatodendritic autoreceptor in raphe serotonergic neurons, it opens GIRK channels to hyperpolarize neurons and set firing rate; genetic deletion nearly doubles raphe firing rate, and selective manipulation of autoreceptor levels causally determines stress resilience and antidepressant responsiveness (PMID:11821026, PMID:20152112, PMID:15306649). Cryo-EM structures reveal that phosphatidylinositol 4-phosphate at the receptor–Gi interface enhances signaling, cholesterol directly shapes the ligand-binding pocket, and structured water molecules in the apo state maintain constitutive activity (PMID:33762731). Transcription is driven by the MAZ/Sp1 promoter complex and repressed by NUDR/DEAF-1 at the C(-1019)G polymorphism—a variant associated with major depression and suicide—while glucocorticoids negatively regulate hippocampal HTR1A transcription and miR-26a-2 post-transcriptionally suppresses autoreceptor levels (PMID:8626793, PMID:14507979, PMID:7769998, PMID:30808545).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1987 High

    Cloning of the HTR1A gene revealed an intronless GPCR with adrenergic receptor homology, establishing the molecular identity of the 5-HT1A receptor for the first time.

    Evidence Molecular cloning via cross-hybridization with β2-adrenergic receptor probe, DNA sequencing

    PMID:3041227

    Open questions at the time
    • No functional data confirming receptor activity
    • Endogenous ligand binding not demonstrated
  2. 1988 High

    Functional expression of the cloned gene confirmed that it encodes a receptor with the full pharmacological profile of the native 5-HT1A site, validating the clone's identity.

    Evidence Transient expression in COS-7 cells with radioligand binding assays

    PMID:3138543

    Open questions at the time
    • Downstream signaling pathways not yet characterized
    • G-protein coupling specificity unknown
  3. 1989 High

    Reconstitution of signaling showed the receptor inhibits adenylyl cyclase and, at higher occupancy, activates phospholipase C—both through pertussis toxin-sensitive G proteins—defining its dual effector coupling.

    Evidence cAMP and inositol phosphate assays in COS-7 and HeLa cells with pertussis toxin treatment

    PMID:2549039

    Open questions at the time
    • Identity of specific Gα subunits unknown
    • In vivo effector pathway relevance not established
  4. 1993 High

    Identification of cell-type-dependent coupling to specific Gαi subunits (Gαi2 vs. Gαi3) explained how the same receptor could produce different signaling outputs in different neuronal populations.

    Evidence Co-immunoprecipitation with Gi-subtype-specific antisera and adenylyl cyclase inhibition in HeLa and CHO-K1 cells

    PMID:8218170

    Open questions at the time
    • Native neuronal Gα coupling preferences not determined
    • Mechanism of cell-type selectivity unclear
  5. 1995 High

    Demonstrating that glucocorticoids negatively regulate HTR1A transcription at the nuclear run-on level revealed a mechanism by which stress hormones modulate serotonergic tone.

    Evidence Nuclear run-on assays, in situ hybridization, adrenalectomy/dexamethasone replacement in rats

    PMID:7769998

    Open questions at the time
    • Glucocorticoid response element not mapped
    • Whether regulation is direct or indirect not resolved
  6. 1996 High

    Characterization of the TATA-less, GC-rich promoter and identification of MAZ and Sp1 as transcriptional activators defined the basal transcriptional machinery for HTR1A expression.

    Evidence DNase I footprinting, reporter assays, MAZ cDNA cloning

    PMID:8626793

    Open questions at the time
    • Cell-type-specific transcriptional regulation not addressed
    • Relationship to in vivo autoreceptor vs. heteroreceptor expression unknown
  7. 2000 High

    Demonstration that methiothepin and spiperone act as inverse agonists established that 5-HT1A receptors possess constitutive activity, with distinct mechanisms of inverse agonism (G-protein-uncoupled vs. inactive coupled state).

    Evidence [35S]GTPγS binding in CHO cells with extended ternary complex modeling

    PMID:10617139

    Open questions at the time
    • Constitutive activity not yet confirmed in native tissue at that time
    • Structural basis of basal activity unknown
  8. 2002 High

    Genetic deletion of 5-HT1A in knockout mice nearly doubled raphe firing rate without compensatory changes in other autoreceptors, providing causal evidence that the autoreceptor is the principal brake on serotonergic neuron activity.

    Evidence Extracellular recordings in dorsal raphe of 5-HT1A KO mice, radioligand release assays

    PMID:11821026

    Open questions at the time
    • Postsynaptic heteroreceptor contributions confounded in global KO
    • Developmental compensation cannot be excluded
  9. 2003 High

    Discovery that the C(-1019)G promoter polymorphism abolishes NUDR/DEAF-1-mediated repression linked a specific transcriptional mechanism to major depression risk, connecting autoreceptor expression levels to psychiatric disease.

    Evidence EMSA, co-IP, stable expression reducing endogenous 5-HT1A, immunohistochemistry, case-control genetic association

    PMID:14507979

    Open questions at the time
    • Causal chain from polymorphism to disease phenotype not fully established
    • Population-level effect size and replication across cohorts debated
  10. 2004 High

    Electrophysiological recordings showed that 5-HT1A activation hyperpolarizes orexin neurons via GIRK channels (~33.8 pS), providing a defined ionic mechanism for serotonergic inhibition of arousal circuits.

    Evidence Whole-cell and single-channel patch clamp in hypothalamic slices, pharmacological blockade, in vivo validation with orexin-ablated mice

    PMID:15306649

    Open questions at the time
    • Contribution to sleep-wake regulation in intact circuitry not quantified
    • Whether GIRK subunit composition differs across 5-HT1A-expressing cell types unresolved
  11. 2005 High

    Demonstration that 5-HT1A activation inhibits NMDA-NR2B currents in PFC via microtubule destabilization and KIF17-dependent trafficking revealed a non-canonical effector pathway linking serotonin to glutamatergic synaptic plasticity.

    Evidence Patch-clamp in PFC slices, KIF17 siRNA, microtubule stability assays, immunocytochemistry

    PMID:15944377

    Open questions at the time
    • Whether this pathway operates at autoreceptors or only heteroreceptors not tested
    • In vivo relevance to cognitive function not established
  12. 2008 High

    Identification of Yif1B as a C-terminal interactor required for dendritic targeting of 5-HT1A established a specific ER/Golgi trafficking mechanism for somatodendritic receptor localization.

    Evidence Yeast two-hybrid, GST pulldown from rat brain, siRNA in primary neurons

    PMID:18685031

    Open questions at the time
    • Whether Yif1B loss affects autoreceptor function in vivo untested
    • Other trafficking partners not explored
  13. 2008 Medium

    FRET-based detection of palmitoylation-dependent homo-oligomers whose conformation changes upon agonist activation revealed that 5-HT1A functions as a dynamic oligomeric complex at the plasma membrane.

    Evidence Multiple FRET techniques in living N1E-115 cells with palmitoylation-deficient mutants

    PMID:18381076

    Open questions at the time
    • Oligomeric stoichiometry and interface not structurally resolved
    • Functional significance of oligomerization for signaling not determined
    • Confirmed in only one cell line
  14. 2010 High

    Region-specific autoreceptor manipulation causally demonstrated that raphe 5-HT1A autoreceptor levels determine stress resilience and antidepressant response, separating autoreceptor from heteroreceptor functions in vivo.

    Evidence Conditional transgenic mice with raphe-specific autoreceptor level manipulation, electrophysiology, behavioral paradigms

    PMID:20152112

    Open questions at the time
    • Molecular mechanism downstream of autoreceptor level changes not detailed
    • Translational relevance to human pharmacotherapy not directly tested
  15. 2010 High

    Genetic disruption of RGS regulation at Gαi2 selectively potentiated 5-HT1A-mediated antidepressant-like behavior, identifying RGS-Gαi2 as a key negative regulator constraining the receptor's therapeutic signaling axis.

    Evidence RGS-insensitive Gαi2 knock-in mice, WAY-100635 blockade, GSK-3β phosphorylation assays

    PMID:20534514

    Open questions at the time
    • Which specific RGS family member(s) are responsible not identified
    • Whether RGS regulation differs between auto- and heteroreceptors unknown
  16. 2019 Medium

    Identification of miR-26a-2 as a direct post-transcriptional repressor of HTR1A in serotonergic neurons added a microRNA-based regulatory layer to autoreceptor expression control, with bidirectional effects on stress resilience.

    Evidence Luciferase reporter assays with Htr1a 5'UTR, serotonergic-neuron-specific transgenic gain/loss-of-function mice, reciprocal genetic rescue

    PMID:30808545

    Open questions at the time
    • Endogenous miR-26a-2 levels in human raphe neurons not measured
    • Interaction with other post-transcriptional regulators not explored
  17. 2021 High

    Cryo-EM structures of 5-HT1A–Gi complexes resolved longstanding questions about how lipids regulate receptor function: PI4P at the G-protein interface enhances signaling, cholesterol shapes ligand selectivity, and structured waters maintain basal activity.

    Evidence Cryo-EM structure determination (apo, 5-HT-bound, aripiprazole-bound), PI4P functional assays, G-protein activation assays

    PMID:33762731

    Open questions at the time
    • Structures determined in detergent/lipid nanodisc — native membrane environment effects not captured
    • Dynamic transitions between active and inactive states not resolved
    • Oligomeric state not visible in structures

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for cell-type-specific Gαi subtype selectivity, the identity of RGS proteins that constrain 5-HT1A signaling in vivo, and whether the oligomeric state observed by FRET is functionally relevant in native neurons.
  • No structure of autoreceptor vs. heteroreceptor conformational differences
  • RGS family member identity at 5-HT1A not determined
  • In vivo functional consequence of oligomerization unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 7 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-112316 Neuronal System 5 R-HSA-74160 Gene expression (Transcription) 3
Partners
DEAF1GNAI2GNAI3GNAO1MAZPSMD7TRIM21YIF1B

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 The HTR1A gene is an intronless gene encoding a G-protein-coupled receptor with structural homology to adrenergic receptors, identified by cross-hybridization with a beta-2 adrenergic receptor probe. Molecular cloning and DNA sequencing Nature High 3041227
1988 The protein product of genomic clone G-21 (HTR1A) transiently expressed in monkey kidney cells displays all typical ligand-binding characteristics of the 5-HT1A receptor, establishing the identity of the cloned gene. Transient expression in COS-7 cells with radioligand binding assays Nature High 3138543
1989 The cloned human 5-HT1A receptor couples to multiple signal transduction pathways via pertussis toxin-sensitive G-proteins: it inhibits adenylyl cyclase (EC50 ~20 nM for 5-HT) and, at higher agonist concentrations, stimulates phospholipase C. No stimulation of adenylyl cyclase was observed. Transient (COS-7) and stable (HeLa) expression, cAMP and inositol phosphate assays, pertussis toxin treatment The Journal of biological chemistry High 2549039
1993 Human 5-HT1A receptors physically and functionally couple to multiple Gi alpha subunits (Gi-alpha1, Gi-alpha2, Gi-alpha3) in a cell-type-dependent manner: Gi-alpha3 predominates in HeLa cells while Gi-alpha2 predominates in CHO-K1 cells. No physical or functional coupling to Gs alpha was detected. Agonist promotes receptor–G protein co-immunoprecipitation. Co-immunoprecipitation, high-affinity agonist binding, adenylyl cyclase inhibition assays with Gi-subtype-specific antisera in two cell lines Biochemistry High 8218170
1996 The 5-HT1A receptor gene contains a TATA-less, GC-rich promoter. Transcription factors MAZ (Pur-1/Zif87) and Sp1 bind to GC-rich elements in the promoter; overexpression of MAZ or Sp1 increases reporter expression, with MAZ being substantially more effective. An initiator-like element was also identified. RNA 5'-end mapping, DNase I footprinting, transient transfection reporter assays, cDNA cloning of MAZ The Journal of biological chemistry High 8626793
2000 Methiothepin and spiperone act as inverse agonists at the 5-HT1A receptor, inhibiting both agonist-stimulated and basal [35S]GTPgammaS binding. Simulations using the extended ternary complex model indicate spiperone stabilizes receptor forms uncoupled from G proteins, while methiothepin may stabilize an inactive receptor form that retains G-protein coupling. [35S]GTPgammaS binding assay in CHO cells expressing human 5-HT1A receptor, GDP/sodium titration, extended ternary complex modeling Journal of neurochemistry High 10617139
2002 Aripiprazole binds with high affinity to recombinant human 5-HT1A receptors and acts as a potent partial agonist, as demonstrated by stimulation of [35S]GTPgammaS binding that is fully blocked by a selective 5-HT1A antagonist. Radioligand binding and [35S]GTPgammaS functional assay in CHO cell membranes expressing human 5-HT1A receptor European journal of pharmacology High 12063084
2003 The C(-1019)G polymorphism in the HTR1A promoter is associated with major depression and suicide. The C(-1019) allele forms a 26 bp palindrome that binds transcription factors NUDR/DEAF-1 and Hes5 to repress the 5-HT1A promoter; the G(-1019) allele abolishes NUDR-mediated repression. Stable NUDR expression in raphe cells reduced endogenous 5-HT1A protein and binding. NUDR co-localizes with 5-HT1A receptors in raphe cells and hippocampal/cortical neurons. EMSA, co-immunoprecipitation, stable cell line expression, radioligand binding, immunohistochemistry, case-control genetic association The Journal of neuroscience High 14507979
2005 Activation of 5-HT1A receptors in PFC pyramidal neurons inhibits NR2B subunit-containing NMDA receptor-mediated currents via a microtubule-dependent mechanism. The effect requires intact microtubule assembly, the kinesin motor KIF17 (which transports NR2B vesicles along dendrites), and CaMKII and MEK/ERK signaling. 5-HT1A activation reduces microtubule stability and decreases surface NR2B subunit density on dendrites. Whole-cell patch-clamp recordings in PFC slices, pharmacological inhibitors, siRNA knockdown of KIF17, immunocytochemistry, biochemical microtubule stability assay The Journal of neuroscience High 15944377
2005 Cannabidiol (CBD) displaces [3H]8-OH-DPAT from the cloned human 5-HT1A receptor in a concentration-dependent manner and acts as a modest-affinity agonist, increasing [35S]GTPgammaS binding and decreasing cAMP levels similarly to serotonin. Radioligand displacement binding assay and [35S]GTPgammaS binding/cAMP assay in cells expressing human 5-HT1A receptor Neurochemical research Medium 16258853
2006 Native rat hippocampal 5-HT1A receptors exhibit constitutive G-protein (Galpha-o) activity in vitro; spiperone and methiothepin act as inverse agonists by reducing basal [35S]GTPgammaS binding to Galpha-o, and these effects are antagonized by WAY100,635 with affinities consistent with the 5-HT1A receptor. Anti-Galpha-o antibody capture coupled to scintillation proximity assay for [35S]GTPgammaS binding in native rat hippocampal membranes Molecular pharmacology Medium 17167032
2008 The C-terminal 17 aa domain of the 5-HT1A receptor interacts with Yif1B (a mammalian homologue of yeast Yif1p involved in ER-to-Golgi vesicular trafficking). This interaction was confirmed by GST pulldown from rat brain extracts and transfected cells. siRNA knockdown of Yif1B in primary neurons specifically prevented targeting of 5-HT1A receptor to distal dendrites without affecting other receptors. Yeast two-hybrid screen, GST pulldown, siRNA knockdown in primary neurons, immunofluorescence co-localization The Journal of neuroscience High 18685031
2008 The 5-HT1A receptor forms homo-oligomers (predominantly dimers) at the plasma membrane of neuroblastoma cells. Agonist stimulation decreases apparent FRET efficiency between CFP/YFP-labeled receptor pairs, suggesting conformational rearrangement of oligomers rather than dissociation. Palmitoylation of the receptor is required for this agonist-induced conformational change, as acylation-deficient mutants fail to show the agonist-mediated FRET decrease. FRET (acceptor photobleaching, fluorescence lifetime, spectral analysis) in living N1E-115 cells; biochemical analysis with palmitoylation-deficient mutants Biochimica et biophysica acta Medium 18381076
2010 Genetic disruption of RGS protein regulation at Galpha-i2 (G184S knock-in mice) selectively potentiates 5-HT1A receptor-mediated antidepressant-like and anxiolytic-like behaviors, and increases cortical/hippocampal GSK-3beta phosphorylation. Both behavioral and biochemical phenotypes are blocked by the 5-HT1A-selective antagonist WAY 100635, placing RGS-Galpha-i2 as a key negative regulator downstream of 5-HT1A receptor signaling. RGS-insensitive Galpha-i2 knock-in mice, behavioral tests, pharmacological blockade with WAY 100635, biochemical phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America High 20534514
2010 Selective manipulation of 5-HT1A autoreceptor levels in raphe nuclei (without affecting postsynaptic heteroreceptors) causally determines raphe 5-HT neuron firing rates, stress resilience, and antidepressant response. 1A-High mice show blunted stress response and no antidepressant behavioral response; reducing autoreceptor levels prior to treatment converts non-responders to responders. Conditional transgenic mice with region-specific autoreceptor level manipulation, electrophysiology, behavioral tests, antidepressant treatment paradigm Neuron High 20152112
2004 Serotonin, acting via 5-HT1A receptors, hyperpolarizes orexin/hypocretin neurons through activation of GIRK channels (single-channel conductance ~33.8 pS). 5-HT1A receptor immunoreactivity was identified on orexin neurons, and WAY100635 blocked the hyperpolarization. Blockade of 5-HT1A receptors in orexin-neuron-intact (but not ablated) mice increased locomotor activity, indicating this pathway tonically inhibits orexin neuron activity. Patch-clamp recordings (whole-cell and single-channel) in hypothalamic slices from orexin-EGFP mice, pharmacology, immunohistochemistry, icv injection with orexin-ablated mouse comparison The Journal of neuroscience High 15306649
2004 5-HT2A receptor activation in the hypothalamic paraventricular nucleus induces heterologous desensitization of co-expressed 5-HT1A receptors, as demonstrated by reduced oxytocin and ACTH responses to 5-HT1A agonist. Intra-PVN microinjection of a 5-HT2A antagonist dose-dependently prevented this desensitization. Double-label immunocytochemistry confirmed co-localization of 5-HT1A and 5-HT2A receptors in individual PVN neuroendocrine cells. In vivo neuroendocrine hormone assays, intra-PVN microinjections, double-label immunocytochemistry The Journal of pharmacology and experimental therapeutics Medium 15064330
2019 miR-26a-2 directly downregulates Htr1a expression in serotonergic neurons (confirmed by reporter assays with the Htr1a 5'UTR). In vivo, miR-26a-2 overexpression in serotonergic neurons improves stress resilience and antidepressant response, effects abrogated by Htr1a overexpression; miR-26a-2 knockdown increases anxiety and impairs antidepressant response, rescued by Htr1a silencing. Luciferase reporter assays, transgenic mouse models with serotonergic-neuron-specific miR-26a-2 overexpression or knockdown, behavioral tests, lentiviral Htr1a manipulation Biochemical and biophysical research communications Medium 30808545
2021 HTR1A antagonism (WAY-100635) upregulates GnRH expression in GT1-7 neurons via an epigenetic mechanism: it reduces CBX4 expression, causing degradation of Polycomb Repressive Complex 1 (PRC1) and loss of H2AK119 ubiquitination at the GnRH promoter. CBX4 downregulation is mediated by suppression of PI3K/Akt and MAPK/ERK pathways. RNA-seq, ChIP-seq for CBX4 and H2AK119ub, co-immunoprecipitation, pharmacological inhibitor studies in GT1-7 cells Molecular therapy. Nucleic acids Medium 34458005
2021 Cryo-EM structures of 5-HT1A receptor in complex with Gi protein were determined in apo state, bound to 5-HT, and bound to aripiprazole. Phosphatidylinositol 4-phosphate (PI4P) is present at the G-protein–5-HT1A interface and increases 5-HT1A-mediated G-protein activity. Cholesterol molecules directly shape the ligand-binding pocket and determine specificity for aripiprazole. Structured water molecules in the apo-receptor binding pocket mimic 5-HT to maintain basal activation. Cryo-EM structure determination, lipid biochemistry (PI4P functional assay), G-protein activation assay Nature High 33762731
2016 Molecular dynamics simulations of the 5-HT1A receptor with two epimers of dihydrofuroaporphine (agonist vs. antagonist) revealed that the agonist mobilizes nearby amino acid residues as molecular switches to form a continuous water channel, whereas the antagonist epimer remains firmly stabilized in the binding pocket without triggering this conformational change. All-atom long-timescale molecular dynamics simulations with molecular interaction fingerprint analysis Angewandte Chemie (International ed. in English) Low 27244650
2022 HTR1A interacts with TRIM21 and PSMD7 (components of the ubiquitin-proteasome pathway) to inhibit TβRII degradation, thereby suppressing TGF-β canonical and non-canonical signaling in triple-negative breast cancer cells. This was demonstrated by co-immunoprecipitation and RNA-seq analysis. Co-immunoprecipitation, siRNA screening, RNA-seq, in vivo xenograft experiments Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 35199941
2012 A subpopulation (~16%) of serotonergic neurons in the dorsal, lateral, and median raphe does not express the somatodendritic 5-HT1A autoreceptor mRNA. These 5-HT1A-negative neurons fire more action potentials upon large depolarizing current injection than 5-HT1A-positive neurons, consistent with lack of autoinhibitory feedback from locally released 5-HT. Histochemistry in ePet1-eGFP and 5-HT1A-iCre/R26R mice, patch-clamp recording followed by single-cell PCR ACS chemical neuroscience Medium 23336048
2002 Genetic deletion of the 5-HT1A autoreceptor in knockout mice nearly doubles the mean firing rate of dorsal raphe 5-HT neurons. No compensatory changes in 5-HT1B, 5-HT1D, or alpha2-adrenergic autoreceptor function were detected in hippocampus or frontal cortex. Extracellular electrophysiological recordings in 5-HT1A knockout mice, radioligand release assays in preloaded brain slices European journal of pharmacology High 11821026
1995 Glucocorticoid hormones negatively regulate transcription of the hippocampal 5-HT1A receptor gene: adrenalectomy increases 5-HT1A mRNA within 1 hour (preceding receptor binding site increases) and elevates transcription rate by 70% in nuclear run-on assays; dexamethasone treatment completely prevents this increase. Adrenalectomy did not alter functional coupling of 5-HT1A receptors to adenylyl cyclase or phospholipase C. In situ hybridization, RNase protection assays, nuclear run-on transcription assays, adrenalectomy/steroid replacement in rats Brain research. Molecular brain research High 7769998

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature genetics 2251 20935630
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2005 Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochemical research 654 16258853
1988 The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature 575 3138543
2003 Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. The Journal of neuroscience : the official journal of the Society for Neuroscience 517 14507979
1987 An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature 492 3041227
2002 The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. European journal of pharmacology 444 12063084
2003 Is there a role for 5-HT1A agonists in the treatment of depression? Biological psychiatry 439 12559651
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2008 Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Molecular psychiatry 350 18982004
2010 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron 343 20152112
1998 Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. The Journal of neuroscience : the official journal of the Society for Neuroscience 336 9736659
1989 Effector coupling mechanisms of the cloned 5-HT1A receptor. The Journal of biological chemistry 272 2549039
2005 Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study. Biological psychiatry 270 16154547
2008 The role of 5-HT(1A) receptors in learning and memory. Behavioural brain research 268 18394726
2004 Reduced serotonin type 1A receptor binding in panic disorder. The Journal of neuroscience : the official journal of the Society for Neuroscience 262 14736842
1988 Presence of three distinct molecular species of Gi protein alpha subunit. Structure of rat cDNAs and human genomic DNAs. The Journal of biological chemistry 256 2834384
2007 Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors. Progress in neurobiology 249 17316955
2004 Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. Biological psychiatry 229 14744462
2010 Brainstem serotonergic deficiency in sudden infant death syndrome. JAMA 228 20124538
1993 WAY100135: a novel, selective antagonist at presynaptic and postsynaptic 5-HT1A receptors. European journal of pharmacology 222 8365456
2010 Poor replication of candidate genes for major depressive disorder using genome-wide association data. Molecular psychiatry 220 20351714
2021 Structural insights into the lipid and ligand regulation of serotonin receptors. Nature 217 33762731
2005 A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans. The Journal of neuroscience : the official journal of the Society for Neuroscience 200 15758168
2001 Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. Neurology 200 11723272
1996 The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1. The Journal of biological chemistry 200 8626793
2004 Investigation of serotonin-related genes in antidepressant response. Molecular psychiatry 192 15052272
2005 Serotonin 5-HT1A receptors regulate NMDA receptor channels through a microtubule-dependent mechanism. The Journal of neuroscience : the official journal of the Society for Neuroscience 187 15944377
2001 The 5-HT1A receptor in schizophrenia: a promising target for novel atypical neuroleptics? Journal of psychopharmacology (Oxford, England) 183 11277607
2003 5-HT2A and 5-HT2C receptors and their atypical regulation properties. Life sciences 175 12650852
2003 Allelic variation in 5-HT1A receptor expression is associated with anxiety- and depression-related personality traits. Journal of neural transmission (Vienna, Austria : 1996) 171 14666415
2003 Regulation of 5-HT1A receptor function in brain following agonist or antidepressant administration. Life sciences 163 12559389
2004 Serotonergic regulation of the orexin/hypocretin neurons through the 5-HT1A receptor. The Journal of neuroscience : the official journal of the Society for Neuroscience 161 15306649
2017 Biomarkers of Suicide Attempt Behavior: Towards a Biological Model of Risk. Current psychiatry reports 159 28470485
2016 The 5-HT1A receptor in Major Depressive Disorder. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 157 26851834
2018 The 5-HT1A receptor: Signaling to behavior. Biochimie 154 31079617
2004 Association of the C(-1019)G 5-HT1A functional promoter polymorphism with antidepressant response. The international journal of neuropsychopharmacology 151 15447813
2006 Response to fluoxetine and serotonin 1A receptor (C-1019G) polymorphism in Taiwan Chinese major depressive disorder. The pharmacogenomics journal 148 16302021
1993 Cell-specific physical and functional coupling of human 5-HT1A receptors to inhibitory G protein alpha-subunits and lack of coupling to Gs alpha. Biochemistry 145 8218170
2004 Limbic reductions of 5-HT1A receptor binding in human temporal lobe epilepsy. Neurology 144 15111672
2008 Transcriptional regulation at a HTR1A polymorphism associated with mental illness. Neuropharmacology 140 18639564
2009 Altered expression of CD4(+)CD25(+) regulatory T cells and its 5-HT(1a) receptor in patients with major depression disorder. Journal of affective disorders 137 19900711
2011 Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness. Molecular brain 121 21619616
2009 Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety. Archives of general psychiatry 120 19124686
2012 Transcriptional regulation of the 5-HT1A receptor: implications for mental illness. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 118 22826341
2006 Increased fear response to contextual cues in mice lacking the 5-HT1A receptor. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 111 15920501
1990 Application of brain microdialysis to study the pharmacology of the 5-HT1A autoreceptor. Journal of neuroscience methods 100 2259248
2014 Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders. CNS neuroscience & therapeutics 94 24935787
2008 Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression. Molecular psychiatry 90 18268499
1998 Alcohol-heightened aggression in mice: attenuation by 5-HT1A receptor agonists. Psychopharmacology 88 9768554
2007 Serotonin-1A receptor gene HTR1A variation predicts interferon-induced depression in chronic hepatitis C. Gastroenterology 84 17408646
2005 [11C]-WAY100635 PET demonstrates marked 5-HT1A receptor changes in sporadic ALS. Brain : a journal of neurology 84 15689356
1990 NAN-190: agonist and antagonist interactions with brain 5-HT1A receptors. Brain research 83 2282513
2004 Decreased 5-HT1A receptor binding in amygdala of schizophrenia. Biological psychiatry 82 15023569
2015 Hippocampal 5-HT1A Receptor and Spatial Learning and Memory. Frontiers in pharmacology 81 26696889
2009 Effect of 5-HT1A gene polymorphisms on antidepressant response in major depressive disorder. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 81 18484082
1992 Evidence for postsynaptic mediation of the hypothermic effect of 5-HT1A receptor activation. British journal of pharmacology 80 1387027
2007 Interaction between 5-HT1A and BDNF genotypes increases the risk of treatment-resistant depression. Journal of neural transmission (Vienna, Austria : 1996) 76 17401528
2004 Desensitization of 5-HT1A receptors by 5-HT2A receptors in neuroendocrine neurons in vivo. The Journal of pharmacology and experimental therapeutics 69 15064330
2004 Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation. Brain research bulletin 69 15145142
1994 Hippocampal serotonin 5-HT1A receptor enhances acetylcholine release in conscious rats. Journal of neurochemistry 68 8158130
2011 Nicotine alters limbic function in adolescent rat by a 5-HT1A receptor mechanism. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 65 21412223
1994 Antiemetic effects of serotonergic 5-HT1A-receptor agonists in Suncus murinus. Japanese journal of pharmacology 64 8028227
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