Cited by 115Cannabis and Cannabinoid ResearchIon Channels and ReceptorsPain Mechanisms and Treatments

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Immunohistochemical localization of anabolic and catabolic enzymes for anandamide and other putative endovanilloids in the hippocampus and cerebellar cortex of the mouse brain

Cristino, L., Starowicz, K., De Petrocellis, L., Morishita, J., Ueda, N., Guglielmotti, V., Di Marzo, V.·2008·Neuroscience

DOI 10.1016/j.neuroscience.2007.11.047

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Abstract

An increasing body of evidence indicates that: 1) the endocannabinoid anandamide (AEA) and other unsaturated N-acylethanolamines (NAEs), 2) 12-(S)-lipoxygenase (12-LOX) products of arachidonic acid, and 3) unsaturated N-acyldopamines (NADAs), act as endogenous ligands of transient receptor potential vanilloid type 1 (TRPV1) channels at intracellular binding sites. AEA is synthesized and released "on demand" in neurons from its membrane precursor, N-arachidonoyl-phosphatidylethanolamine, by an N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), and is inactivated by intracellular hydrolysis by fatty acid amide hydrolase (FAAH), whereas catechol-O-methyl-transferase (COMT) was suggested to inactivate NADAs. However, it is not known whether these enzymes or 12-LOX co-localize to any extent with TRPV1 receptors in the brain. In this study we used immunohistochemical techniques (single peroxidase and double immunofluorescence staining), and analyzed the localization of the TRPV1 channel in mouse hippocampal and cerebellar neurons with respect to NAPE-PLD, FAAH, 12-LOX and COMT. Cycloxygenase-2 (COX-2), another putative AEA-degrading enzyme, was also studied. Co-localization between TRPV1 and either NAPE-PLD or FAAH, COX-2, 12-LOX and COMT was found in Ammon's horn (CA3) hippocampal pyramidal neurons and (with the exception of 12-LOX) in some Purkinje cells. At the cellular level, both anabolic and catabolic enzymes appeared as fine grains with immunoperoxidase labeling and were observed in the somatodendritic compartment of CA3 pyramidal cells as well as (with the exception of 12-LOX) in the cytoplasm of Purkinje neurons, in which FAAH and COX-2 immunoreactivities were, however, preferentially localized in the large extension of the dendritic arbor. Our data agree with the hypothesis that, in potential "endovanillergic" neurons, endogenous TRPV1 agonists, and AEA in particular, act as intracellular mediators by being produced from and/or degraded by the same mouse brain cells that express TRPV1 receptors.

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Authors: Cristino, L., Starowicz, K., De Petrocellis, L., Morishita, J., Ueda, N., Guglielmotti, V., & Di Marzo, V.
Affiliations: Institute of Applied Science and Intelligent Systems (IT)
Istituto di Chimica Biomolecolare (IT)
Kagawa University (JP)
ORCID: Cristino, L.
Starowicz, K.
Morishita, J.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2008-02
Volume: 151
Issue: 4
Pages: 955-968
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2007.11.047
OpenAlex: W2024356032
Cited by: 115
References: 70
Citations by year: 2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 11 · 2016: 3 · 2015: 5 · 2014: 8 · 2013: 8 · 2012: 11
FWCI: 7.53
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Keywords: anandamide, endocannabinoids, endovanilloids, TRPV1, fatty acid amide hydrolase, 12-lipoxygenase, catechol-O-methyltransferase, cyclooxygenase-2, N-acylethanolamines, hippocampus, cerebellar cortex, Purkinje cells, CA3 pyramidal cells, enzyme colocalization
MeSH terms: Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Arachidonate 12-Lipoxygenase, Catechol O-Methyltransferase, Cerebellar Cortex, Glutamate Decarboxylase, Hippocampus, Male, Neurons, Phospholipase D, TRPV Cation Channels, Mice, Cyclooxygenase 2

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Immunohistochemical localization of anabolic and catabolic enzymes for anandamide and other putative endovanilloids in the hippocampus and cerebellar cortex of the mouse brain

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