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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide.
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Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide.

机译：肥大细胞表达对大麻素和棕榈酰乙醇酰胺具有不同敏感性的外周大麻素受体。

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摘要

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").
机译：肥大细胞是在粘膜和结缔组织以及神经系统中发现的多功能骨髓来源的细胞，它们在组织炎症和神经免疫相互作用中起重要作用。关于内源性分子和能够调节肥大细胞活化的机制知之甚少。已提出在外周组织中发现的棕榈酰乙醇酰胺起局部下丘脑的作用，能够下调肥大细胞的活化和炎症。相关的N-酰基酰胺，花生四烯酸的乙醇酰胺发生在大脑中，是中央大麻素受体（CB1）的候选内源性激动剂。由于在外周组织中发现了第二种大麻素受体（CB2），因此研究了肥大细胞上CB2受体的可能存在及其与N-酰基酰胺的相互作用。在这里，我们报告肥大细胞表达基因和功能性CB2受体蛋白，对肥大细胞激活具有负调节作用。尽管棕榈酰乙醇酰胺和阿南酰胺都与CB2受体结合，但只有前者在体外下调肥大细胞的活化。进一步，棕榈酰乙醇酰胺以及活性大麻素的功能作用被anandamide有效地拮抗。结果表明：（i）激动剂结合后，外围大麻素CB2受体控制肥大细胞活化并因此控制炎症； （ii）棕榈酰乙醇酰胺与anandamide不同，它起肥大细胞中CB2受体的内源性激动剂的作用； （iii）天然存在的分子对肥大细胞的调节活性增强了拟南芥类局部炎症拮抗作用（ALIA）的机制； （iv）棕榈酰乙醇酰胺及其衍生物可以提供专门针对肥大细胞的抗炎治疗策略（“ ALIAmides”）。

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