ArticleScience (New York, N.Y.)2022
Angiotensin-converting enzyme gates brain circuit-specific plasticity via an endogenous opioid.
Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Gene-level analysis reveals the genetic aetiology and therapeutic targets of schizophrenia.Nature human behaviour · 2025Pooled it
- Alzheimer's disease-linked ACE variants increase ACE1 catalytic activity and production of angiotensin II.The Journal of biological chemistry · 2026Article
- Integrative Multi-Omics Mendelian Randomization Reveals Oxidative Stress Mechanisms in Major Depressive Disorder, Bipolar Disorder, and Schizophrenia.Antioxidants (Basel, Switzerland) · 2026Article
- Inhibition of the angiotensin-converting enzyme N-terminal catalytic domain prevents endogenous opioid degradation in brain tissue.JCI insight · 2026Article
- Role of Angiotensin-Converting Enzyme in Cognitive Aging: Evidence from Preclinical and Clinical Studies.Frontiers in drug discovery · 2026Article
- Molecular basis of domain-specific angiotensin I-converting enzyme inhibition by the antihypertensive drugs enalaprilat, ramiprilat, trandolaprilat, quinaprilat and perindoprilat.The FEBS journal · 2026Article
- Gain of Alternative Allele Expression of LINC02449 at rs149707223 in Schizophrenia and Bipolar Disorder: Inducing Synaptic Transmission and Behavioral Deficits in Mice.Nature communications · 2025Article
- Exploiting the angiotensin-converting enzyme pathway to augment endogenous opioid signaling.Communications biology · 2025Article
- Effects of Angiotensin II Receptor 1 Inhibition by LCZ696 on the Acquisition and Relapse of Methamphetamine-Associated Contextual Memory.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Highly sensitive in vivo detection of dynamic changes in enkephalins following acute stress in mice.eLife · 2025Article
- A review of the effects of different types of social behaviors on the recruitment of neuropeptides and neurotransmitters in the nucleus accumbens.Frontiers in neuroendocrinology · 2025Review
- Structural basis for the inhibition of cystathionine-β-synthase by isoflurane and its role in anaesthesia-induced social dysfunction in mice.British journal of anaesthesia · 2025Article
- Article
- The role of mu-opioid receptors in pancreatic islet α-cells.Journal of molecular endocrinology · 2025Article
- Neuronal ACE1 knockout disrupts the hippocampal renin angiotensin system leading to memory impairment and vascular loss in normal aging.Neurobiology of disease · 2024Article
- Modulation of endogenous opioid signaling by inhibitors of puromycin-sensitive aminopeptidase.European journal of medicinal chemistry · 2024Article
- Current understanding of the link between angiotensin-converting enzyme and pain perception.Drug discovery today · 2024Review
- The role of mu-opioid receptors in pancreatic islet alpha cells.bioRxiv : the preprint server for biology · 2024Article
- Modulation of endogenous opioid signaling by inhibitors of puromycin sensitive aminopeptidase.bioRxiv : the preprint server for biology · 2024Article
- The central renin-angiotensin system: A genetic pathway, functional decoding, and selective target engagement characterization in humans.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Angiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce angiotensin II. In the brain, ACE is especially abundant in striatal tissue, but the function of ACE in striatal circuits remains poorly understood. We found that ACE degrades an unconventional enkephalin heptapeptide, Met-enkephalin-Arg-Phe, in the nucleus accumbens of mice. ACE inhibition enhanced µ-opioid receptor activation by Met-enkephalin-Arg-Phe, causing a cell type-specific long-term depression of glutamate release onto medium spiny projection neurons expressing the Drd1 dopamine receptor. Systemic ACE inhibition was not intrinsically rewarding, but it led to a decrease in conditioned place preference caused by fentanyl administration and an enhancement of reciprocal social interaction. Our results raise the enticing prospect that central ACE inhibition can boost endogenous opioid signaling for clinical benefit while mitigating the risk of addiction.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.