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Tytuł:
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The fatty acid amide hydrolase inhibitor URB597 modulates splenic catecholamines in chronically stressed female and male rats.
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Autorzy:
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Ferizovic H; Department of Molecular Biology and Endocrinology, 'Vinča' Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
Spasojevic N; Department of Molecular Biology and Endocrinology, 'Vinča' Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
Stefanovic B; Department of Molecular Biology and Endocrinology, 'Vinča' Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
Jankovic M; Department of Molecular Biology and Endocrinology, 'Vinča' Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
Dronjak S; Department of Molecular Biology and Endocrinology, 'Vinča' Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. Electronic address: .
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Źródło:
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International immunopharmacology [Int Immunopharmacol] 2020 Aug; Vol. 85, pp. 106615. Date of Electronic Publication: 2020 May 21.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
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MeSH Terms:
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Amidohydrolases/*antagonists & inhibitors
Anti-Anxiety Agents/*pharmacology
Benzamides/*pharmacology
Carbamates/*pharmacology
Catecholamines/*metabolism
Spleen/*drug effects
Spleen/*metabolism
Stress, Physiological/*drug effects
Animals ; Anti-Anxiety Agents/therapeutic use ; Anxiety/drug therapy ; Benzamides/therapeutic use ; Carbamates/therapeutic use ; Catechol O-Methyltransferase/metabolism ; Catecholamine Plasma Membrane Transport Proteins/metabolism ; Endocannabinoids/pharmacology ; Female ; Interleukin-10/blood ; Interleukin-6/blood ; Male ; Monoamine Oxidase/metabolism ; Neuroprotective Agents/pharmacology ; Open Field Test/drug effects ; Phenylethanolamine N-Methyltransferase/metabolism ; Rats, Wistar ; Sex Factors ; Spleen/immunology ; Stress, Physiological/physiology
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Contributed Indexing:
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Keywords: Catecholamines; Endocannabinoids; Stress; The spleen; URB597
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Substance Nomenclature:
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0 (Anti-Anxiety Agents)
0 (Benzamides)
0 (Carbamates)
0 (Catecholamine Plasma Membrane Transport Proteins)
0 (Catecholamines)
0 (Endocannabinoids)
0 (Il6 protein, rat)
0 (Interleukin-6)
0 (Neuroprotective Agents)
0 (cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester)
130068-27-8 (Interleukin-10)
EC 1.4.3.4 (Monoamine Oxidase)
EC 2.1.1.28 (Phenylethanolamine N-Methyltransferase)
EC 2.1.1.6 (Catechol O-Methyltransferase)
EC 3.5.- (Amidohydrolases)
EC 3.5.1.- (fatty-acid amide hydrolase)
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Entry Date(s):
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Date Created: 20200525 Date Completed: 20210430 Latest Revision: 20210430
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Update Code:
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20240105
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DOI:
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10.1016/j.intimp.2020.106615
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PMID:
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32447219
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The changes in sympathetic innervations in lymphoid organs could be a key factor in immune dysregulation. The endocannabinoid system has been shown to exhibit potent immunomodulatory effects that may differ between males and females, representing a potential therapeutic target for peripheral and central inflammatory disorders. Thus, in the present study, an examination was made of the effect of fatty acid amide hydrolase inhibitor URB597 treatment on splenic catecholamine content, synthesis, uptake and degradation in chronically unpredictably stressed (CUS) female and male rats. The results show that CUS increases anxiety-like behaviors and that URB597 had an anxiolytic effect on chronically stressed animals of both sexes. CUS induced the expression of plasma interleukin - 6 (IL-6), interleukin - 10 (IL-10) and IL-6 in the spleen, whereas the expression of IL-10 was reduced in the spleen of both sexes. URB597 treatment did not cause changes in IL-6 in plasma or the spleen, whereas it increased IL-10 in the spleen in CUS animals of both sexes. CUS caused a significant depletion of noradrenaline content in the spleen of female rats and a reduction in noradrenaline uptake in the spleen of female rats, while stressed males had a small but insignificant decrease of splenic noradrenaline levels and an enhanced uptake. The FAAH inhibitor URB597 enhances reduced noradrenaline content, affecting its uptake directly at the level of the spleen. It gives rise to the possibility that endocannabinoids exert a neurorestorative effect on the sympathetic nerve system and cell-mediated immune responses in the spleen of chronically stressed rats.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
