Affinage

ADCY1

Adenylate cyclase type 1 · UniProt Q08828

Length
1119 aa
Mass
123.4 kDa
Annotated
2026-04-28
68 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADCY1 (adenylyl cyclase 1/AC1) is a Ca²⁺/calmodulin-stimulated adenylyl cyclase that converts ATP to cAMP in response to intracellular Ca²⁺ elevations, functioning as a coincidence detector that couples neuronal Ca²⁺ influx through NMDA receptors and α7 nicotinic acetylcholine receptors to compartmentalized cAMP/PKA and ERK signaling, thereby controlling synaptic long-term potentiation, fear extinction, and nociceptive sensitization (PMID:25937212, PMID:28721398, PMID:32145934, PMID:38389098). AC1 activity is further regulated by Gαs-dependent heterologous sensitization following persistent Gαi/o-coupled receptor activation, a mechanism implicated in opioid tolerance, and its transcription is directly controlled by CUX2 (PMID:15361543, PMID:36242624). Beyond the CNS, AC1 generates Ca²⁺-stimulated cAMP in cardiac sinoatrial node cells to modulate the pacemaker current I(f) and biological heart rate, and in inner-ear hair cells where it is required for mechanotransduction and hearing (PMID:17540702, PMID:22753192, PMID:24482543). Biallelic loss-of-function mutations in ADCY1 cause autosomal recessive hearing impairment in humans (PMID:24482543).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 Medium

    Identifying the molecular basis of the barrelless mouse phenotype established that ADCY1 loss-of-function disrupts neural circuit refinement, providing the first genetic proof that AC1 is required for activity-dependent brain development.

    Evidence Northern blot showing ETn retrotransposon insertion abolishes normal Adcy1 transcript in barrelless mice

    PMID:10656922

    Open questions at the time
    • Mechanism by which transcript loss causes barrel cortex defect not resolved
    • Protein-level confirmation not shown
  2. 2004 High

    Demonstrating that Gαs interacts directly with AC1 to produce heterologous sensitization after persistent Gαi/o signaling revealed a second mode of AC1 regulation beyond Ca²⁺/calmodulin stimulation, relevant to drug tolerance mechanisms.

    Evidence Site-directed mutagenesis of AC1 (F293L, Y973S) and dominant-negative Gαs constructs with D1/D2 receptor activation in transfected cells

    PMID:15361543

    Open questions at the time
    • Structural basis of Gαs-AC1 interaction not resolved
    • In vivo relevance to opioid sensitization not tested in this study
  3. 2005 Medium

    Mapping the spatiotemporal expression of AC1 across mouse brain development revealed transient early expression in sensory relay nuclei and progressive restriction to hippocampus, cortex, and cerebellum, providing the anatomical framework for its roles in synaptic plasticity and sensory map formation.

    Evidence In situ hybridization across embryonic and postnatal mouse brain time points

    PMID:15844169

    Open questions at the time
    • Expression data only; no functional perturbation at developmental stages
    • Protein-level spatial confirmation not performed
  4. 2007 High

    Demonstrating that AC1 is selectively expressed in sinoatrial node cells where it modulates pacemaker current I(f) through Ca²⁺-stimulated cAMP production established a cardiac function for AC1 outside the nervous system.

    Evidence RT-PCR, immunoblotting, confocal immunofluorescence, and patch-clamp electrophysiology with BAPTA and MDL inhibitor in guinea-pig SAN cells

    PMID:17540702

    Open questions at the time
    • Genetic loss-of-function in cardiac pacemaker not tested
    • Human cardiac relevance not established
  5. 2012 Medium

    Overexpression of AC1 in canine heart generated biological pacing activity, validating AC1 as sufficient to drive cAMP-dependent automaticity and demonstrating translational potential for biological pacemaker therapy.

    Evidence Adenoviral AC1 gene transfer in AV-blocked dogs with Holter ECG recordings

    PMID:22753192

    Open questions at the time
    • Long-term stability of biological pacing not assessed
    • Endogenous AC1 contribution to native pacemaking not isolated
  6. 2014 High

    Discovery that a human ADCY1 nonsense mutation causes recessive hearing impairment, combined with zebrafish knockdown phenocopying hair cell dysfunction, established AC1 as essential for auditory mechanotransduction and identified ADCY1 as a deafness gene.

    Evidence Whole-exome sequencing (p.Arg1038*), immunofluorescence in cochlea, COS-7 truncation assays, zebrafish morpholino with FM1-43 uptake and startle response

    PMID:24482543

    Open questions at the time
    • Precise cAMP-dependent mechanism in hair cell stereocilia unknown
    • Whether other ADCY1 mutations cause deafness not explored
  7. 2014 Medium

    Showing that AC1 loss increases ipsilateral corticospinal projections and enhances locomotor recovery after spinal cord injury revealed a developmental role for AC1 in axon guidance that constrains adult neural repair capacity.

    Evidence Anterograde and retrograde tracing in Adcy1brl mice with BMS behavioral scoring after spinal cord injury

    PMID:24418466

    Open questions at the time
    • Single lab study
    • Molecular targets downstream of AC1 in corticospinal development not identified
  8. 2015 High

    Establishing that α7 nAChR activation stimulates cAMP via AC1 in a Ca²⁺-dependent manner, leading to synapsin phosphorylation, identified AC1 as the enzymatic link coupling cholinergic Ca²⁺ signals to presynaptic neurotransmitter release regulation.

    Evidence FRET-based cAMP biosensor, BAPTA chelation, selective AC1 inhibitor CB-6673567, siRNA knockdown, and synapsin phosphorylation in hippocampal neurons

    PMID:25937212

    Open questions at the time
    • In vivo behavioral consequence of α7-AC1 coupling not tested
    • Whether other Ca²⁺ sources access AC1 in this context unclear
  9. 2017 High

    Demonstrating that FMRP normally represses ADCY1 translation and that genetic reduction of Adcy1 rescues ERK/PI3K signaling, spine morphology, and behavioral deficits in Fragile X model mice positioned AC1 overactivity as a central mediator of Fragile X pathophysiology.

    Evidence Fmr1 KO mice, polyribosome fractionation, genetic Adcy1 reduction, ERK1/2 and PI3K phosphorylation, dendritic spine morphology, and behavioral assays

    PMID:28218269

    Open questions at the time
    • Whether AC1 reduction is therapeutically viable in human FXS not tested
    • Relative contribution of AC1 vs. other FMRP targets unknown
  10. 2017 High

    Identifying AC1 as required for methylglyoxal-evoked hyperalgesia via a TRPA1→AC1 spinal pathway, and showing AC1 contributes to insular cortex LTP via NMDAR-dependent postsynaptic mechanisms, consolidated AC1's role as a pain sensitization hub at both spinal and cortical levels.

    Evidence AC1 and TRPA1 knockout mice with behavioral and immunohistochemical readouts; whole-cell patch-clamp LTP in insular cortex slices with selective AC1 inhibitors

    PMID:28721398 PMID:29270106

    Open questions at the time
    • Spinal AC1 downstream effectors (PKA vs. Epac) not fully dissected in 2017 study
    • Insular cortex findings from single lab with pharmacological approach only
  11. 2018 Medium

    Showing AC1 translocates to plasma membrane signalosomes containing GPCRs, CFTR, and TMEM16A upon receptor stimulation in airway epithelia revealed a non-neuronal compartmentalized signaling role for AC1.

    Evidence siRNA knockdown of ADCY1, patch-clamp Cl⁻ currents, confocal localization, co-immunoprecipitation in airway epithelial cells

    PMID:29331508

    Open questions at the time
    • Single lab study
    • No reciprocal Co-IP or proximity labeling for signalosome
    • In vivo airway relevance not tested
  12. 2019 High

    Delineating a complete spinal TRPA1→AC1→Epac cascade in diabetic neuropathy mice identified Epac as the critical cAMP effector downstream of AC1 in pain sensitization, distinguishing this pathway from canonical PKA-mediated mechanisms.

    Evidence db/db diabetic mice, intrathecal pharmacological inhibitors targeting each cascade component, Ca²⁺ imaging in dorsal horn neurons, behavioral assays

    PMID:30807826

    Open questions at the time
    • Whether Epac vs. PKA selectivity is specific to MG-TRPA1 pathway or general to AC1 pain signaling unknown
  13. 2020 High

    Establishing that AC1 maintains latent nociceptive sensitization downstream of NMDA receptors after nerve injury via an NPY-Y1→NMDAR→AC1→TRPA1/TRPV1 cascade defined AC1 as the enzymatic node sustaining chronic pain vulnerability beyond the acute injury phase.

    Evidence AC1 deletion mutant mice, NPY conditional knockdown, intrathecal pharmacology with MK-801/NB001/TRP blockers, reinstatement assays

    PMID:32145934

    Open questions at the time
    • Whether AC1 blockade provides lasting analgesia vs. temporary suppression unclear
    • Epigenetic or transcriptional regulation of AC1 in chronic pain not explored
  14. 2021 Medium

    Identification of ADCY1 as a direct miR-19a target in pancreatic β-cells whose knockdown impairs glucose-stimulated insulin secretion revealed AC1-dependent cAMP signaling as part of the islet secretory machinery exploited by pancreatic cancer exosomes.

    Evidence Luciferase reporter assay, siRNA knockdown of Adcy1, GSIS assay in MIN6 cells and primary mouse islets

    PMID:34512170

    Open questions at the time
    • Single lab study
    • Endogenous AC1 contribution to normal GSIS vs. other adenylyl cyclases not established
  15. 2022 Medium

    ChIP and reporter assays showing CUX2 directly binds and activates the ADCY1 promoter identified the first transcription factor controlling ADCY1 expression, with functional consequences for tumor suppression in glioma.

    Evidence ChIP assay, dual-luciferase reporter, gain/loss-of-function in glioma cells, xenograft model

    PMID:36242624

    Open questions at the time
    • Whether CUX2 regulates ADCY1 in normal neurons not tested
    • Other transcriptional regulators of ADCY1 remain unknown
  16. 2024 Medium

    Demonstrating that AC1 inhibition selectively enhances fear extinction relearning in aged mice without affecting memory formation or acute nociception defined a narrow therapeutic window for AC1 modulators in age-related cognitive flexibility.

    Evidence Trace and auditory fear conditioning/extinction with oral hNB001 in adult and aged mice, multiple behavioral controls

    PMID:38389098

    Open questions at the time
    • Molecular mechanism of extinction selectivity not resolved
    • Single lab, single inhibitor
  17. 2025 Medium

    Multiple converging studies established AC1 as a cortical sensitization hub in migraine, mediating NMDA-GluN2B/AMPA-GluA1 phosphorylation and LTP in the ACC and insular cortex; separately, AC1-dependent cAMP signaling was shown essential for neural maturation in human forebrain organoids, and AC1/KATP coupling was linked to opioid tolerance.

    Evidence Rat migraine models with ACC electrophysiology and NB001 injection; human forebrain organoids with ADCY1 inhibition/overexpression; mouse genetic AC1 reduction with opioid withdrawal and KATP channel assays

    PMID:37235050 PMID:38760739 PMID:39974972 PMID:40471331

    Open questions at the time
    • Migraine and organoid findings each from single labs
    • KATP-AC1 coupling data from preprint only
    • Human in vivo validation of AC1 inhibition for migraine or opioid tolerance absent

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of Ca²⁺/calmodulin activation and Gαs sensitization of AC1, the full spectrum of compartment-specific AC1 effectors (PKA vs. Epac vs. ERK) across cell types, and whether selective AC1 inhibition can achieve therapeutic benefit in pain, opioid tolerance, or neuropsychiatric conditions without disrupting essential functions in hearing and cardiac pacing.
  • No high-resolution structure of AC1 with calmodulin
  • No clinical trials of selective AC1 inhibitors
  • Relative contributions of AC1 vs. AC8 in overlapping expression domains not fully resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0009975 cyclase activity 6 GO:0140657 ATP-dependent activity 3
Localization
GO:0005886 plasma membrane 2 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-112316 Neuronal System 6
Partners
CFTRCUX2FMRPHCN2TMEM16ATRPA1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 AC1 (ADCY1) is selectively expressed in guinea-pig sino-atrial node (SAN) cells but not ventricular muscle, where it localizes to the membrane and modulates the pacemaker current I(f) through Ca2+-stimulated cAMP production; buffering cytosolic Ca2+ with BAPTA shifted I(f) activation in the hyperpolarizing direction and abolished further inhibition by AC inhibitor MDL, demonstrating functional Ca2+-stimulated AC activity in pacemaking. RT-PCR, immunoblotting, confocal immunofluorescence, patch-clamp electrophysiology with pharmacological inhibitors (MDL 12330A, IBMX, BAPTA-AM, forskolin) The Journal of physiology High 17540702
2014 ADCY1 loss-of-function (nonsense mutation p.Arg1038*) in humans causes recessive hearing impairment by disrupting the enzymatic catalytic domain and calmodulin-stimulation; ADCY1 localizes to the cytoplasm of supporting cells, hair cells, cochlear hair cell nuclei, and stereocilia; the carboxyl tail of ADCY1 is essential for localization to actin-based microvilli as shown in COS-7 cell experiments; zebrafish adcy1b morphants show loss of FM1-43 dye uptake and startle response, indicating hair cell dysfunction. Whole-exome sequencing, immunofluorescence localization, COS-7 cell overexpression/truncation assays, zebrafish morpholino knockdown with FM1-43 uptake and behavioral assays Human molecular genetics High 24482543
2015 Activation of α7 nicotinic acetylcholine receptors (nAChRs) increases intracellular cAMP levels in hippocampal neurons via AC1 in a Ca2+-dependent manner; the Ca2+ chelator BAPTA and selective AC1 inhibitor CB-6673567 both abolished the choline-induced cAMP rise, and siRNA-mediated deletion of AC1 blocked the effect; downstream, AC1 activation led to phosphorylation of synapsin to regulate neurotransmitter release. FRET-based cAMP biosensor live-cell imaging, pharmacological inhibition (MLA antagonist, BAPTA, selective AC1 inhibitor CB-6673567), siRNA knockdown, synapsin phosphorylation assay Neuropharmacology High 25937212
2017 In Fmr1 knockout neurons (model of Fragile X syndrome), ADCY1 mRNA translation is enhanced due to loss of FMRP, leading to excess ADCY1 protein and aberrant ERK1/2 and PI3K signaling; genetic reduction of Adcy1 normalizes ERK1/2/PI3K signaling, attenuates excessive protein synthesis, and corrects dendritic spine abnormality; behavioral deficits (repetitive behavior, defective social interaction, audiogenic seizures) were also rescued. Fmr1 knockout mice, polyribosome fractionation/mRNA translation assay, genetic Adcy1 reduction, ERK1/2 and PI3K phosphorylation assays, dendritic spine morphology, behavioral assays, pharmacological inhibition with NB001 Nature communications High 28218269
2018 ADCY1 is translocated to specific plasma membrane domains containing GPCRs, CFTR, and TMEM16A in airway epithelial cells upon GPCR stimulation, producing compartmentalized Ca2+/cAMP signals that mediate crosstalk between TMEM16A and CFTR; ADCY1 knockdown disrupted this signalosome assembly and attenuated functional coupling. siRNA knockdown of ADCY1 and GPCRs, electrophysiology (patch clamp for Cl- currents), immunofluorescence/confocal membrane localization, co-immunoprecipitation/pulldown Cellular signalling Medium 29331508
2004 Gαs-AC1 interaction is required for expression of AC1 sensitization following persistent Gαi/o-coupled receptor activation; Gαs-insensitive AC1 mutants (F293L and Y973S) retain Ca2+ and forskolin sensitivity but show markedly reduced heterologous sensitization; dominant-negative Gαs mutants disrupted D1-Gαs signaling but did not alter D2 agonist-induced sensitization, indicating sensitization involves Gαs-AC1 interactions downstream of Gαi. Site-directed mutagenesis of AC1, dominant-negative Gαs constructs, D1/D2 receptor activation in transfected cells, adenylyl cyclase activity assays Molecular pharmacology High 15361543
2012 AC1 (Ca2+-stimulated adenylyl cyclase) expressed in left bundle branches of atrioventricular-blocked dogs generates biological pacing by elevating cAMP; AC1 overexpression increased basal beating rate, reduced escape time, decreased dependence on electronic backup pacing, and shifted autonomic responsiveness toward parasympathetic modulation; combined AC1+HCN2 expression further enhanced pacing rate. Adenoviral gene transfer in vivo (dog AV block model), Holter ECG recordings, heart rate variability analysis Circulation Medium 22753192
2017 AC1 is required for methylglyoxal (MG)-evoked hyperalgesia but not acute nociceptive behaviors; AC1 knockout abolished MG-induced heat and mechanical hyperalgesia; pharmacological inhibition of TRPA1 reduced MG-evoked spinal p-ERK and nociception, establishing a TRPA1-AC1 sensitization mechanism in painful diabetic neuropathy. AC1 knockout mice, TRPA1 knockout mice, intrathecal pharmacology (HC030031, TRPA1 antagonist), immunohistochemistry for p-ERK in spinal cord, behavioral assays (licking/lifting, heat/mechanical hyperalgesia, conditioned place avoidance) Frontiers in neuroscience High 29270106
2019 Methylglyoxal activates a spinal TRPA1-AC1-Epac signaling cascade to facilitate painful diabetic neuropathy in db/db mice; pharmacological or genetic inhibition of TRPA1, AC1, PKA, or Epac blocked MG-evoked hypersensitivity; intrathecal GERP10 (MG scavenger), HC030031 (TRPA1 inhibitor), NB001 (AC1 inhibitor), or HJC-0197 (Epac inhibitor) all attenuated hypersensitivity in db/db mice. db/db mouse model of type 2 diabetes, intrathecal pharmacological inhibitors, genetic inhibition, Ca2+ mobilization imaging in dorsal horn neurons, behavioral assays Neurobiology of disease High 30807826
2017 AC1 contributes to LTP in the insular cortex (IC); postsynaptic BAPTA blocked IC LTP induction; pharmacological inhibition of AC1 (but not AC8) blocked LTP; the LTP was NMDAR-dependent and expressed postsynaptically (no change in PPR), with involvement of Ca2+-permeable AMPARs and PKMζ in expression. Whole-cell patch-clamp LTP recording in acute mouse brain slices, postsynaptic BAPTA infusion, selective AC1/AC8 inhibitors, paired-pulse ratio analysis Heliyon Medium 28721398
2020 Spinal AC1 acts downstream of NMDA receptors (NMDAR→AC1 pathway) to maintain latent sensitization of nociceptive neurons after peripheral nerve injury; AC1 deletion mutant mice showed absence of BIBO3304-induced reinstatement of mechanical hypersensitivity and conditioned place aversion; intrathecal NB001 (AC1 inhibitor) or TRPV1/TRPA1 blockers also prevented reinstatement, establishing NPY-Y1→NMDAR→AC1→TRPA1/TRPV1 signaling cascade. AC1 deletion mutant mice, NPY conditional knockdown (NPYtet/tet mice), intrathecal pharmacology (MK-801, NB001, AMG9801, HC030031), conditioned place aversion/preference assays, mechanical hypersensitivity testing Neuropeptides High 32145934
2000 An ETn retrotransposon insertion in an intron of the mouse Adcy1 gene causes loss of the normal Adcy1 transcript and generates aberrant shorter transcripts due to abnormal RNA splicing and termination, confirming a loss-of-function mutation underlying the barrelless (Adcy1brl) phenotype. Northern blot analysis, phylogenetic analysis of ETn LTR sequences Mammalian genome Medium 10656922
2005 AC1 (and AC8) exhibit spatially and temporally distinct expression patterns in mouse brain development; AC1 is broadly expressed beginning before E13 with transient expression in striatum, dorsal thalamus, trigeminal nuclei, Purkinje cells, hippocampal interneurons, and retinal ganglion cells, peaking early postnatally and then restricting to hippocampus, cerebral cortex, and cerebellar granule cells after P15. In situ hybridization across embryonic and postnatal mouse brain time points The Journal of comparative neurology Medium 15844169
2014 Loss of AC1 (barrelless mutation) in mice results in increased ipsilateral corticospinal axons in dorsal and ventral medial funiculi, increased density of corticospinal motor neurons in motor cortex layer V, and enhanced locomotor recovery after spinal cord injury, indicating AC1 regulates late phases of corticospinal tract development. Anterograde and retrograde tracing of corticospinal tract in Adcy1brl mice, BMS behavioral scoring after spinal cord injury Brain research Medium 24418466
2021 MiR-19a secreted by pancreatic cancer cells via exosomes directly targets ADCY1 (and EPAC2) in pancreatic β-cells to disrupt glucose-stimulated insulin secretion; luciferase reporter assays confirmed ADCY1 as a direct miR-19a target; knockdown of ADCY1 impaired insulin secretion from MIN6 cells and primary mouse islets. Exosome isolation, luciferase reporter assay (miR-19a target validation), siRNA knockdown of Adcy1, glucose-stimulated insulin secretion assay in MIN6 cells and primary islets International journal of biological sciences Medium 34512170
2022 CUX2 transcription factor binds the ADCY1 promoter and enhances ADCY1 transcription; ChIP and dual-luciferase assays confirmed CUX2 enrichment at the ADCY1 promoter; overexpression of ADCY1 mimicked CUX2-mediated suppression of glioma cell proliferation, migration, and invasion in vitro and in vivo. Dual-luciferase reporter assay, ChIP assay, gain/loss-of-function in glioma cells (CCK8, transwell, colony formation), xenograft mouse model Experimental brain research Medium 36242624
2023 ADCY1 regulates decidualization of human endometrial stromal cells (HESCs) through the cAMP signaling pathway; siRNA knockdown of INHBB reduced ADCY1 expression and cAMP production, impairing decidualization markers; INHBB and ADCY1 expression positively correlated in RIF patient endometria; forskolin (direct AC activator) rescued the INHBB-knockdown decidualization defect. RNA-seq, siRNA knockdown of INHBB, cAMP measurement, RT-qPCR and immunofluorescence of decidual markers, Pearson correlation analysis, forskolin rescue experiment Journal of assisted reproduction and genetics Medium 36913138
2025 AC1 inhibition with NB001 in the anterior cingulate cortex (ACC) of migraine rats reduced CGRP expression, alleviated periorbital mechanical thresholds, and attenuated anxiety behaviors; NMDA GluN2B receptor phosphorylation and excitatory synaptic transmission were elevated in the insular cortex of migraine rats and reduced by AC1 inhibitor hNB001. Rat chronic migraine model (dural inflammatory soup), stereotaxic ACC injection of hNB001, intraperitoneal injection, whole-cell patch-clamp recording, immunofluorescence and western blotting for CGRP and GluN2B, von Frey filament testing, open field and elevated plus maze The journal of headache and pain Medium 38760739
2024 AC1 inhibitor hNB001 selectively enhanced relearning during fear extinction in aged mice but did not affect fear memory induction, expression, or recent/remote auditory fear memory; AC1 inhibition also had no effect on acute nociception, motor function, or anxiety in adult or aged mice. Trace and auditory fear conditioning/extinction in adult and aged mice, hNB001 acute and chronic oral administration, behavioral assays (von Frey, rotarod, open field) Molecular brain Medium 38389098
2025 AC1 inhibition (hNB001) in the ACC reduces cortical LTP, reverses elevated NMDA GluN2B and AMPA GluA1 phosphorylation, and attenuates both presynaptic glutamate release and postsynaptic AMPAR/NMDAR responses in a migraine rat model; synaptic LTP was occluded in migraine rats, consistent with AC1-dependent cortical sensitization mediating migraine-related pain and anxiety. Whole-cell patch-clamp recording, biochemical phosphorylation assays, mEPSC recording, LTP occlusion protocol, intra-ACC injection of NB001, behavioral assays (von Frey, open field) iScience Medium 37235050
2025 Montelukast (MTK) exposure in human forebrain organoids downregulates ADCY1 expression, reduces cAMP levels and neuroactivity, and causes neural maturation defects; these phenotypes were recapitulated by the selective ADCY1 inhibitor ST034307 and partially rescued by ADCY1 overexpression, establishing ADCY1-mediated cAMP signaling as the mechanistic hub for MTK's neuropsychiatric effects. Human forebrain organoids, RNA-seq, pharmacological ADCY1 inhibition (ST034307), ADCY1 overexpression, cAMP measurement, neuroactivity assays Cellular and molecular life sciences Medium 40471331
2025 Genetic reduction of AC1 and simultaneous upregulation of KATP channel subunits (SUR1 or Kir6.2) attenuated morphine tolerance and reduced naloxone-precipitated withdrawal in mice; in vitro, inhibition of AC1 (or EPAC) enhanced KATP channel activity after chronic morphine treatment; chronic opioid-induced cAMP overshoot (heterologous sensitization) was blocked by AC1 inhibition. Genetic AC1 reduction in mice, naloxone-precipitated withdrawal assays, EPAC2-GFP-cAMP FRET biosensor in SH-SY5Y and HEK cells, thallium flux KATP channel activity assay, mouse dorsal root ganglia recordings bioRxivpreprint Medium 39974972
2024 AC1 inhibition blocked the rapid synaptic potentiation of Schaffer collateral-CA1 synapses induced by ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) in hippocampal slices; HNK required protein kinase A (PKA) activity and AC1 (but not AC5) activity for this rapid potentiation, which then primed synaptic plasticity to lower the LTP threshold. Extracellular electrophysiology in hippocampal slices, pharmacological inhibitors of AC1 and AC5, PKA inhibitors, in vitro incubation model with behavioral pharmacological validation bioRxivpreprint Medium bio_10.1101_2024.10.18.619152
2024 Lysosomal Ca2+ signaling via NAADP pathway contributes to α-adrenergic (phenylephrine)-stimulated cAMP production in atrial myocytes via AC1 and AC8; double knockout of Adcy1 and Adcy8 in mice reduced positive chronotropic and inotropic responses to phenylephrine, decreased Ca2+ transient amplitude in isolated atrial myocytes, and decreased cytosolic cAMP levels, with the NAADP pathway inhibition no longer affecting cAMP in double-KO cells. Adcy1/Adcy8 double-knockout mouse model, NAADP pathway inhibitors (BZ-194, SAN4825, bafilomycin A1), cAMP measurement in neonatal atrial myocytes, Ca2+ transient measurement, ex vivo atrial contractility bioRxivpreprint Medium bio_10.1101_2024.11.25.625232

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Mutations in the AXR3 gene of Arabidopsis result in altered auxin response including ectopic expression from the SAUR-AC1 promoter. The Plant journal : for cell and molecular biology 291 8811856
1994 Characterization of the auxin-inducible SAUR-AC1 gene for use as a molecular genetic tool in Arabidopsis. Plant physiology 111 8159792
2007 Ca2+-stimulated adenylyl cyclase isoform AC1 is preferentially expressed in guinea-pig sino-atrial node cells and modulates the I(f) pacemaker current. The Journal of physiology 100 17540702
1992 Regulation of the activities of African cassava mosaic virus promoters by the AC1, AC2, and AC3 gene products. Virology 80 1585657
1996 Multiple regions of the Arabidopsis SAUR-AC1 gene control transcript abundance: the 3' untranslated region functions as an mRNA instability determinant. The EMBO journal 61 8612592
2011 Enzymological analysis of the tumor suppressor A-C1 reveals a novel group of phospholipid-metabolizing enzymes. Journal of lipid research 50 21880860
2018 Compartmentalized crosstalk of CFTR and TMEM16A (ANO1) through EPAC1 and ADCY1. Cellular signalling 48 29331508
2017 Enhanced expression of ADCY1 underlies aberrant neuronal signalling and behaviour in a syndromic autism model. Nature communications 44 28218269
2015 Activation of α7 nicotinic acetylcholine receptors increases intracellular cAMP levels via activation of AC1 in hippocampal neurons. Neuropharmacology 42 25937212
2012 Ca(2+)-stimulated adenylyl cyclase AC1 generates efficient biological pacing as single gene therapy and in combination with HCN2. Circulation 42 22753192
2005 A novel thermoacidophilic endoglucanase, Ba-EGA, from a new cellulose-degrading bacterium, Bacillus sp.AC-1. Applied microbiology and biotechnology 42 16142468
1998 Evidence that the autoimmune antigen myelin basic protein (MBP) Ac1-9 binds towards one end of the major histocompatibility complex (MHC) cleft. The Journal of experimental medicine 42 9565642
2014 Adenylate cyclase 1 (ADCY1) mutations cause recessive hearing impairment in humans and defects in hair cell function and hearing in zebrafish. Human molecular genetics 39 24482543
2019 A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer. Journal of Cancer 38 31839819
2007 Hairpin RNA-mediated strategies for silencing of tomato leaf curl virus AC1 and AC4 genes for effective resistance in plants. Oligonucleotides 36 17638528
2005 Spatiotemporal localization of the calcium-stimulated adenylate cyclases, AC1 and AC8, during mouse brain development. The Journal of comparative neurology 35 15844169
2019 Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes. Neurobiology of disease 33 30807826
2021 Pancreatic cancer-derived exosomal microRNA-19a induces β-cell dysfunction by targeting ADCY1 and EPAC2. International journal of biological sciences 32 34512170
1999 Gender differences in protection from EAE induced by oral tolerance with a peptide analogue of MBP-Ac1-11. Journal of neuroscience research 30 10723054
1996 Mutational analysis of the putative nicking motif in the replication-associated protein (AC1) of bean golden mosaic geminivirus. Molecular plant-microbe interactions : MPMI 30 8810074
2020 Silencing AC1 of Tomato leaf curl virus using artificial microRNA confers resistance to leaf curl disease in transgenic tomato. Plant cell reports 28 32860518
2017 Methylglyoxal Requires AC1 and TRPA1 to Produce Pain and Spinal Neuron Activation. Frontiers in neuroscience 28 29270106
2016 Biocontrol activity of Paenibacillus polymyxa AC-1 against Pseudomonas syringae and its interaction with Arabidopsis thaliana. Microbiological research 28 26946374
2011 Engineering cotton (Gossypium hirsutum L.) for resistance to cotton leaf curl disease using viral truncated AC1 DNA sequences. Virus genes 27 21327530
2022 Antibacterial and anti-biofilm activities of probiotic Lactobacillus curvatus BSF206 and Pediococcus pentosaceus AC1-2 against Streptococcus mutans. Microbial pathogenesis 26 35167954
2001 Isolation, characterization, and chromosome mapping of a human A-C1 Ha-Ras suppressor gene (HRASLS). Cytogenetics and cell genetics 26 11474175
1997 Regulatory activity exerted by the SAUR-AC1 promoter region in transgenic plants. Plant molecular biology 25 9278170
2017 Calcium-stimulated adenylyl cyclase subtype 1 (AC1) contributes to LTP in the insular cortex of adult mice. Heliyon 24 28721398
1995 Mutational analysis of a putative NTP-binding domain in the replication-associated protein (AC1) of bean golden mosaic geminivirus. Virology 23 7645202
2015 p39R861-4, A Type 2 A/C2 Plasmid Carrying a Segment from the A/C1 Plasmid RA1. Microbial drug resistance (Larchmont, N.Y.) 20 26167918
2007 Transcriptional profiling of human monocytes reveals complex changes in the expression pattern of inflammation-related genes in response to the annexin A1-derived peptide Ac1-25. Journal of leukocyte biology 20 17855500
1985 The monoclonal antibody AC1.59 defines a new polymorphic determinant on HLA-DR molecules. Tissue antigens 18 2412306
2022 Circ-LTBP1 is involved in doxorubicin-induced intracellular toxicity in cardiomyocytes via miR-107/ADCY1 signal. Molecular and cellular biochemistry 16 35076816
2020 Neuropeptide Y tonically inhibits an NMDAR➔AC1➔TRPA1/TRPV1 mechanism of the affective dimension of chronic neuropathic pain. Neuropeptides 16 32145934
2010 Tomato leaf curl Kerala virus (ToLCKeV) AC3 protein forms a higher order oligomer and enhances ATPase activity of replication initiator protein (Rep/AC1). Virology journal 16 20546567
2007 Molecular and biochemical characterization of Ba-EGA, a cellulase secreted by Bacillus sp. AC-1 from Ampullaria crosseans. Applied microbiology and biotechnology 15 17453195
2021 Long non-coding RNA DPP10-AS1 exerts anti-tumor effects on colon cancer via the upregulation of ADCY1 by regulating microRNA-127-3p. Aging 13 33744851
2000 The suppressive effect of TGF-beta on IL-12-mediated immune modulation specific to a peptide Ac1-11 of myelin basic protein (MBP): a mechanism involved in inhibition of both IL-12 receptor beta1 and beta2. Journal of neuroimmunology 12 10900337
2024 Alleviation of migraine related pain and anxiety by inhibiting calcium-stimulating AC1-dependent CGRP in the insula of adult rats. The journal of headache and pain 11 38760739
2022 LncRNA H19 acts as miR-301a-3p sponge to alleviate lung injury in mice with sepsis by regulating Adcy1. Immunopharmacology and immunotoxicology 10 35438054
2021 Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer. Acta pharmaceutica Sinica. B 10 35530157
2004 Using molecular tools to dissect the role of Galphas in sensitization of AC1. Molecular pharmacology 10 15361543
2000 ETn insertion in the mouse Adcy1 gene: transcriptional and phylogenetic analyses. Mammalian genome : official journal of the International Mammalian Genome Society 10 10656922
2022 Electroacupuncture Alleviates Thalamic Pain in Rats by Suppressing ADCY1 Protein Upregulation. Pain physician 9 35793187
2021 Evaluation of calcium-sensitive adenylyl cyclase AC1 and AC8 mRNA expression in the anterior cingulate cortex of mice with spared nerve injury neuropathy. Neurobiology of pain (Cambridge, Mass.) 9 35005298
2004 DFNB44, a novel autosomal recessive non-syndromic hearing impairment locus, maps to chromosome 7p14.1-q11.22. Human heredity 9 15583425
1999 A small number of residues in the class II molecule I-Au confer the ability to bind the myelin basic protein peptide Ac1-11. Proceedings of the National Academy of Sciences of the United States of America 9 9874795
2019 Mechanism of LncRNA FOXC2-AC1 promoting lung cancer metastasis by regulating miR-107. European review for medical and pharmacological sciences 8 30720176
1983 Purification and properties of the inhibitory protein isolated from Lactobacillus acidophilus AC1. Microbios 8 6417455
2023 MiR-1281 is involved in depression disorder and the antidepressant effects of Kai-Xin-San by targeting ADCY1 and DVL1. Heliyon 7 36938448
2025 Ginsenoside Rg1 alleviates cognitive impairment in vascular dementia by modulating Adcy1/Kdr-mediated cholinergic synapse and PI3K-AKT pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 6 40424986
2019 RNA silencing of South African cassava mosaic virus in transgenic cassava expressing AC1/AC4 hp- RNA induces tolerance. Biotechnology reports (Amsterdam, Netherlands) 6 31763196
2014 Establishment of a radial glia-like mouse fetal hypothalamic neural stem cell line (AC1) able to differentiate into neuroendocrine cells. Neurogenesis (Austin, Tex.) 6 28255570
1997 Induction of a heterogeneous TCR repertoire in (PL/JXSJL/J)F1 mice by myelin basic protein peptide Ac1-11 and its analog Ac1-11[4A]. Molecular immunology 6 9444977
2023 Inhibiting neuronal AC1 for treating anxiety and headache in the animal model of migraine. iScience 5 37235050
2023 Downregulated INHBB in endometrial tissue of recurrent implantation failure patients impeded decidualization through the ADCY1/cAMP signalling pathway. Journal of assisted reproduction and genetics 4 36913138
2014 Lack of adenylate cyclase 1 (AC1): consequences on corticospinal tract development and on locomotor recovery after spinal cord injury. Brain research 4 24418466
2012 Characterization of a Ca2+/calmodulin-dependent AC1 adenylyl cyclase in a non-neuronal tissue, the blowfly salivary gland. Cell calcium 4 22633849
2023 Sustained metabolic benefits of ΔTRTX-Ac1, a tarantula venom-derived peptide, when administered together with exenatide in high-fat fed mice. Diabetes, obesity & metabolism 3 37818589
1993 Cytopathology caused by the AC-1 isolate of Marek's disease virus in the feather follicle epidermis. Avian pathology : journal of the W.V.P.A 3 18671018
2023 Anti-Tumoural [NHC(thiolato)] Gold(I) Complexes Derived from HIF-1α Inhibitor AC1-004 Target the Mitochondrial Redox System and Show Antiangiogenic Effects in vivo. ChemPlusChem 2 37161701
2022 CUX2 prevents the malignant progression of gliomas by enhancing ADCY1 transcription. Experimental brain research 2 36242624
2021 Properties of corn-expressed carbohydrase AC1 in swine diets and its effects on apparent ileal digestibility, performance, hematology, and serum chemistry. Heliyon 2 34401579
2025 Lacticaseibacillus rhamnosus AC1 Aggravates Bone Loss in a Male Rat Model of Deoxycorticosterone Acetate (DOCA)-Salt-Induced Osteoporosis. Nutrients 1 41156451
2024 Selective enhancement of fear extinction by inhibiting neuronal adenylyl cyclase 1 (AC1) in aged mice. Molecular brain 1 38389098
2025 Inhibition of adenylyl cyclase 1 (AC1) and exchange protein directly activated by cAMP (EPAC) restores ATP-sensitive potassium (KATP) channel activity after chronic opioid exposure. bioRxiv : the preprint server for biology 0 39974972
2025 The ADCY1-mediated cAMP signaling pathway mediates functional effects of montelukast treatment in brain organoids. Cellular and molecular life sciences : CMLS 0 40471331
2024 The Role of ADCY1 in Regulating the Sensitivity of Platinum-Based Chemotherapy in NSCLC. Pharmaceuticals (Basel, Switzerland) 0 39338283