ArticlePsychopharmacology2008
Use of preproenkephalin knockout mice and selective inhibitors of enkephalinases to investigate the role of enkephalins in various behaviours.
Article in Psychopharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- Contribution of the Opioid System to the Antidepressant Effects of Fluoxetine.Biological psychiatry · 2022Article
- The role of enkephalinergic systems in substance use disorders.Frontiers in systems neuroscience · 2022Review
- Reply to Zhuang et al.: Potential side effects of positive allosteric modulators of the mu-opioid receptor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Dual Enkephalinase Inhibitors and Their Role in Chronic Pain Management.Current pain and headache reports · 2021Review
- Allostery at opioid receptors: modulation with small molecule ligands.British journal of pharmacology · 2018Review
- Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain.Scientific reports · 2016Article
- TGF-β and opioid receptor signaling crosstalk results in improvement of endogenous and exogenous opioid analgesia under pathological pain conditions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Enkephalin knockdown in the basolateral amygdala reproduces vulnerable anxiety-like responses to chronic unpredictable stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
- Cocaine dysregulates opioid gating of GABA neurotransmission in the ventral pallidum.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Opioid receptors: distinct roles in mood disorders.Trends in neurosciences · 2013Review
- In vivo visualization of delta opioid receptors upon physiological activation uncovers a distinct internalization profile.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain.Nature reviews. Drug discovery · 2012Review
- Satb1 ablation alters temporal expression of immediate early genes and reduces dendritic spine density during postnatal brain development.Molecular and cellular biology · 2012Article
- The learned safety paradigm as a mouse model for neuropsychiatric research.Nature protocols · 2010Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleThe most simple and efficient method to study the physiological role of enkephalins is to increase the lifetime of these endogenous opioid peptides by inhibiting their inactivating enzymes. Enkephalins are degraded by the concomitant action of two metallopeptidases: neutral endopeptidase (NEP, EC3.4.21.11) and aminopeptidase N (APN, EC3.4.11.2), both enzymes releasing inactive metabolites.
objectivesPotent dual inhibitors have been developed, such as RB101. However, NEP and APN have a broad specificity and can cleave various peptides in vitro. Therefore, it was essential to investigate the specific involvement of enkephalins in the various pharmacological responses induced by dual inhibitors. MATERIALS AND
methodsWe compared the pharmacological responses induced by RB101 in wild-type and preproenkephalin-deficient mice (Penk1-/-) using several behavioural assays.
resultsIn all the tests used (hot plate test, force swim test, castor-oil-induced diarrhoea), RB101 induced strong effects in wild-type animals, whereas slight effects were observed in Penk1-/- animals. These residual effects are blocked by pre-administration of the opioid antagonist naloxone, supporting the involvement of the opioid receptors in the responses observed.
conclusionsThe pharmacological effects induced by dual inhibitors acting on both NEP and APN are mainly due to the protection of the endogenous enkephalins at supraspinal and peripheral levels. It could be speculated that the residual effects observed in Penk1-/- mice after RB101 administration could be due to the direct action of other opioid peptides or through an indirect effect involving the protection of other peptide substrates of NEP or APN, as substance P or angiotensin.
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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.