Cited by 633Cannabis and Cannabinoid ResearchMast cells and histamineInflammatory mediators and NSAID effects

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Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide

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Facci, L, Dal Toso, R, Romanello, S, Buriani, A, Skaper, S D, Leon, A·1995·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.92.8.3376PMC PMC42169

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Abstract

Mast cells are multifunctional bone marrow-derived cells found in mucosal and connective tissues and in the nervous system, where they play important roles in tissue inflammation and in neuroimmune interactions. Very little is known about endogenous molecules and mechanisms capable of modulating mast cell activation. Palmitoylethanolamide, found in peripheral tissues, has been proposed to behave as a local autacoid capable of downregulating mast cell activation and inflammation. A cognate N-acylamide, anandamide, the ethanolamide of arachidonic acid, occurs in brain and is a candidate endogenous agonist for the central cannabinoid receptor (CB1). As a second cannabinoid receptor (CB2) has been found in peripheral tissues, the possible presence of CB2 receptors on mast cells and their interaction with N-acylamides was investigated. Here we report that mast cells express both the gene and a functional CB2 receptor protein with negative regulatory effects on mast cell activation. Although both palmitoylethanolamide and anandamide bind to the CB2 receptor, only the former downmodulates mast cell activation in vitro. Further, the functional effect of palmitoylethanolamide, as well as that of the active cannabinoids, was efficiently antagonized by anandamide. The results suggest that (i) peripheral cannabinoid CB2 receptors control, upon agonist binding, mast cell activation and therefore inflammation; (ii) palmitoylethanolamide, unlike anandamide, behaves as an endogenous agonist for the CB2 receptor on mast cells; (iii) modulatory activities on mast cells exerted by the naturally occurring molecule strengthen a proposed autacoid local inflammation antagonism (ALIA) mechanism; and (iv) palmitoylethanolamide and its derivatives may provide antiinflammatory therapeutic strategies specifically targeted to mast cells ("ALIAmides").

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Authors: Facci, L., Dal Toso, R., Romanello, S., Buriani, A., Skaper, S. D., & Leon, A.
Affiliations: Researchlife, Castelfranco Veneto (TV), Italy.
ORCID: Buriani, A
Skaper, S D
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1995-04-11
Volume: 92
Issue: 8
Pages: 3376-3380
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.92.8.3376
PMC: PMC42169
OpenAlex: W1998941878
Cited by: 632
References: 43
Citations by year: 2026: 4 · 2025: 8 · 2024: 14 · 2023: 11 · 2022: 10 · 2021: 13 · 2020: 16 · 2019: 24 · 2018: 13 · 2017: 19 · 2016: 16 · 2015: 11 · 2014: 19 · 2013: 24 · 2012: 28
FWCI: 23.55
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Keywords: mast cells, CB2 receptor, anandamide, palmitoylethanolamide, mast cell activation, inflammation, anti-inflammatory therapy, neuroimmune interactions
MeSH terms: Amides, Animals, Arachidonic Acids, Base Sequence, Cannabinoids, Cell Membrane, Cells, Cultured, Ethanolamines, Inflammation, Male, Mast Cells, Molecular Sequence Data, Morpholines, Naphthalenes, Palmitic Acids, Receptors, Drug, Receptors, Cell Surface, RNA, Messenger, Down-Regulation, Rats, Wistar, Molecular Mimicry, Receptors, Cannabinoid, Receptor, Cannabinoid, CB2, Benzoxazines, Rats, Polyunsaturated Alkamides, Endocannabinoids

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Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide

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