Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide
| Autor: | Alberta Leon, Laura Facci, S Romanello, A Buriani, Stephen D. Skaper, R Dal Toso |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Cannabinoid receptor Polyunsaturated Alkamides Morpholines Receptors Drug medicine.medical_treatment Molecular Sequence Data Down-Regulation Receptors Cell Surface Arachidonic Acids Palmitic Acids Naphthalenes Pharmacology Biology Receptor Cannabinoid CB2 chemistry.chemical_compound medicine Cannabinoid receptor type 2 Animals Ethanolamide Mast Cells RNA Messenger Rats Wistar Receptors Cannabinoid Cells Cultured Inflammation Palmitoylethanolamide Multidisciplinary Base Sequence Cannabinoids Cell Membrane Molecular Mimicry Anandamide Amides Endocannabinoid system Benzoxazines Rats Interleukin 33 chemistry Ethanolamines lipids (amino acids peptides and proteins) Cannabinoid Endocannabinoids Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 92:3376-3380 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.92.8.3376 |
| Popis: | 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"). |
| Databáze: | OpenAIRE |
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