Anti-inflammatory dopamine- and serotonin-based endocannabinoid epoxides reciprocally regulate cannabinoid receptors and the TRPV1 channel

Arnold, William R.; Carnevale, Lauren N.; Xie, Zili; Baylon, Javier L.; Tajkhorshid, Emad; Hu, Hongzhen; Das, Aditi

doi:10.1038/s41467-021-20946-6

Cited by 20 publications

(7 citation statements)

References 69 publications

(107 reference statements)

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“…Based on the presented results, it may be concluded that in stromal cells from ectopic endometrium of ovarian cysts, NADA cytotoxicity is characterized by a typical CB1-mediated apoptosis pathway [ 44 ], including downstream ceramide and ROS production leading to caspase-9/-3 activation and mitochondrial dysfunction. Taken together with the previous findings on the NADA pronounced analgesic and anti-inflammatory effects [ 19 , 45 ] and our data on the higher NADAs specificity to stromal cells from endometriotic ovarian cysts, these properties may be considered as a positive factor for further research of these compounds as possible therapeutic agents for endometriosis treatment.…”

Section: Discussionsupporting

confidence: 88%

N-Acyl Dopamines Induce Apoptosis in Endometrial Stromal Cells from Patients with Endometriosis

Gamisonia

Yushina

Fedorova-Gogolina

et al. 2021

IJMS

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Endometriosis is characterized by the formation and development of endometrial tissues outside the uterus, based on an imbalance between proliferation and cell death, leading to the uncontrolled growth of ectopic foci. The potential target for the regulation of these processes is the endocannabinoid system, which was found to be involved in the migration, proliferation, and survival of tumor cells. In this paper, we investigated the effect of endocannabinoid-like compounds from the N-acyl dopamine (NADA) family on the viability of stromal cells from ectopic and eutopic endometrium of patients with ovarian endometriosis. N-arachidonoyldopamine, N-docosahexaenoyldopamine, and N-oleoyldopamine have been shown to have a five-times-more-selective cytotoxic effect on endometrioid stromal cells. To study the mechanisms of the toxic effect, inhibitory analysis, measurements of caspase-3/9 activity, reactive oxygen species, and the mitochondrial membrane potential were performed. It was found that NADA induced apoptosis via an intrinsic pathway through the CB1 receptor and downstream serine palmitoyltransferase, NO synthase activation, increased ROS production, and mitochondrial dysfunction. The higher selectivity of NADA for endometriotic stromal cells and the current lack of effective drug treatment can be considered positive factors for further research of these compounds as possible therapeutic agents against endometriosis.

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Section: Discussionsupporting

confidence: 88%

N-Acyl Dopamines Induce Apoptosis in Endometrial Stromal Cells from Patients with Endometriosis

Gamisonia

Yushina

Fedorova-Gogolina

et al. 2021

IJMS

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“…The endocannabinoid N-arachidonoyl-dopamine (NADA), which is highly expressed in the striatum, hippocampus, and cerebellum, activates TRPV1, induces the release of substance P and calcitonin gene-related peptide from dorsal spinal cord slices, and enhances hippocampal paired-pulse depression [380]. NADA and its epoxide metabolites also act as an agonist for the CB1 and CB2 receptors and show anti-inflammatory activities [337,[381][382][383]. Other dopamine-related endocannabinoids include N-oleoyldopamine (OLDA), N-palmitoyldopamine (PALDA), and N-stearoyldopamine (STEARDA) [384].…”

Section: Other Endocannabinoids and Endocannabinoid-like Compoundsmentioning

confidence: 99%

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Sionov

Steinberg

2022

Biomedicines

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Antibiotic resistance has become an increasing challenge in the treatment of various infectious diseases, especially those associated with biofilm formation on biotic and abiotic materials. There is an urgent need for new treatment protocols that can also target biofilm-embedded bacteria. Many secondary metabolites of plants possess anti-bacterial activities, and especially the phytocannabinoids of the Cannabis sativa L. varieties have reached a renaissance and attracted much attention for their anti-microbial and anti-biofilm activities at concentrations below the cytotoxic threshold on normal mammalian cells. Accordingly, many synthetic cannabinoids have been designed with the intention to increase the specificity and selectivity of the compounds. The structurally unrelated endocannabinoids have also been found to have anti-microbial and anti-biofilm activities. Recent data suggest for a mutual communication between the endocannabinoid system and the gut microbiota. The present review focuses on the anti-microbial activities of phytocannabinoids and endocannabinoids integrated with some selected issues of their many physiological and pharmacological activities.

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“…Our previous publication suggested that the transient receptor potential cation channel subfamily V member 1 (TRPV1), a Ca 2+ permeable ion channel, including related molecules, was increased in the inflamed mice DRG and SC. Thus, TRPV1 and associated molecules were reported as inflammatory biomarkers in both peripheral sites and the brain 19 , 39 . In this study, we showed that pCaMKIIα and related nociceptive molecules were all increased in the CFA-induced inflammatory pain model.…”

Section: Discussionmentioning

confidence: 99%

Optogenetic modulation of electroacupuncture analgesia in a mouse inflammatory pain model

Hsiao

Liao

Lin

2022

Sci Rep

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Peripheral tissue damage and associated inflammation can trigger neuroplastic changes in somatic pain pathways, such as reduced neuronal firing thresholds and synaptic potentiation, that ultimately lead to peripheral sensitization and chronic pain. Electroacupuncture (EA) can relieve chronic inflammatory pain, but the underlying mechanisms are unknown, including the contributions of higher pain centers such as somatosensory cortex (SSC). We investigated these mechanisms using optogenetic modulation of SSC activity in a mouse inflammatory pain model. Injection of Complete Freund's Adjuvant into the hind paw reliably induced inflammation accompanied by reduced mechanical and thermal pain thresholds (hyperalgesia) within three days (mechanical: 1.54 ± 0.13 g; thermal: 3.94 ± 0.43 s). Application of EA produced significant thermal and mechanical analgesia, but these responses were reversed by optogenetic activation of SSC neurons, suggesting that EA-induced analgesia involves modulation of central pain pathways. Western blot and immunostaining revealed that EA also attenuated CaMKIIα signaling in the dorsal root ganglion, central spinal cord, SSC, and anterior cingulate cortex (ACC). In contrast, optogenetic activation of the SSC induced CaMKIIα signaling in SSC and ACC. These findings suggest that AE can relieve inflammatory pain by suppressing CaMKIIα-dependent plasticity in cortical pain pathways. The SSC and ACC CaMKIIα signaling pathways may be valuable therapeutic targets for chronic inflammatory pain treatment.

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Anti-inflammatory dopamine- and serotonin-based endocannabinoid epoxides reciprocally regulate cannabinoid receptors and the TRPV1 channel

Cited by 20 publications

References 69 publications

N-Acyl Dopamines Induce Apoptosis in Endometrial Stromal Cells from Patients with Endometriosis

N-Acyl Dopamines Induce Apoptosis in Endometrial Stromal Cells from Patients with Endometriosis

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Optogenetic modulation of electroacupuncture analgesia in a mouse inflammatory pain model

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