Department of Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinca", National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Pharmacology. 2022;107(1-2):81-89. doi: 10.1159/000519332. Epub 2021 Nov 18.
The present study examined the effects of fatty acid amide hydrolase inhibitor URB597 on the level of plasma catecholamine and their content, synthesis, and degradation in the adrenal medulla of male and female rats subjected to chronic unpredictable stress (CUS).
Male and female Wistar rats were exposed to the 6 weeks of CUS and treated intraperitoneally with either 0.3 mg/kg/day of URB597 or vehicle in the last 2 weeks of stress protocol. Catecholamines' plasma levels and catecholamines' levels in adrenal medulla were examined using Elabscience ELISA kits. Western blot analysis was used to detect the protein in the medulla.
The results of our experiment showed that adrenal weights and catecholamine of unstressed control were higher in females and that CUS induced further enlargement of adrenal glands and catecholamine content and its synthesis compared to male rats. CUS caused an increase of plasma norepinephrine and depletion of norepinephrine content as well as unchanged synthesis and degradation of catecholamine in the adrenal medulla of male rats. URB597 reduced enlarged adrenals and catecholamine content and its synthesis in stressed female rats. URB597 reduces increased plasma norepinephrine and restores its content in the adrenal medulla, unchanging the expression of enzyme synthesis, while reduced protein levels of monoamine oxidase A in male rats are exposed to CUS.
Our results support the role of endocannabinoids as an antistress mechanism that inhibits elevated adrenomedullary activation and promotes its recovery to baseline in both male and female stressed rats.
本研究考察了脂肪酸酰胺水解酶抑制剂 URB597 对慢性不可预测应激（CUS）雄性和雌性大鼠血浆儿茶酚胺及其肾上腺髓质含量、合成和降解的影响。
雄性和雌性 Wistar 大鼠接受 6 周 CUS，并在应激方案的最后 2 周内每天腹膜内给予 0.3mg/kg/天的 URB597 或载体。使用 Elabscience ELISA 试剂盒检测血浆儿茶酚胺水平和肾上腺髓质儿茶酚胺水平。使用 Western blot 分析检测髓质中的蛋白质。
我们的实验结果表明，未受应激对照的雌性大鼠肾上腺重量和儿茶酚胺较高，而 CUS 诱导雄性大鼠肾上腺进一步增大以及儿茶酚胺含量和合成增加。CUS 导致雄性大鼠血浆去甲肾上腺素增加，去甲肾上腺素含量耗竭，而肾上腺髓质儿茶酚胺的合成和降解不变。URB597 减少应激雌性大鼠的肿大肾上腺和儿茶酚胺含量及其合成。URB597 减少 CUS 暴露的雄性大鼠中升高的血浆去甲肾上腺素并恢复其在肾上腺髓质中的含量，而不改变酶合成的表达，同时降低单胺氧化酶 A 的蛋白水平。
我们的结果支持内源性大麻素作为一种抗应激机制的作用，该机制抑制升高的肾上腺髓质激活并促进其在应激雄性和雌性大鼠中恢复到基线水平。
