TRPV1 Activation by Anandamide via a Unique Lipid Pathway

Muller, Chanté; Lynch, Diane L.; Hurst, Dow P.; Reggio, Patricia H.

doi:10.1021/acs.jcim.1c00893

Cited by 8 publications

(3 citation statements)

References 22 publications

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“…In addition to acting on CB1 and CB2, AEA activates the ionotropic TRPV1 channel, resulting in the opening of the ion channel and Ca 2+ influx [312,[326][327][328][329][330][331], the Gprotein-coupled receptor GPR55 [332,333], and the cation channel TRPA1 [334], while it inhibits the TRPM8 channel [334]. In addition, AEA activates PPARγ, and 2-AG activates PPARα [335].…”

Section: Endogenous Receptors For Aea and 2-agmentioning

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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Section: Endogenous Receptors For Aea and 2-agmentioning

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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“…The naphthyl moiety at the end of the tail displays pi-pi interactions with both Y487 and Y445 (Figure 2B). The additional interactions of 1288208 could aid in the stability of the ligand in the tunnel from an external standpoint, allowing the headgroup more time in the tunnel, potentially triggering channel activation as previously hypothesized from MD simulations (Muller et al, 2020(Muller et al, , 2021.…”

Section: Cross-agonist Virtual Screeningmentioning

confidence: 81%

Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators

Morales¹,

Muller

Jagerovic³

et al. 2022

Front. Mol. Biosci.

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Both metabotropic (CBRs) and ionotropic cannabinoid receptors (ICRs) have implications in a range of neurological disorders. The metabotropic canonical CBRs CB1 and CB2 are highly implicated in these pathological events. However, selective targeting at CB2 versus CB1 offers optimized pharmacology due to the absence of psychoactive outcomes. The ICR transient receptor potential vanilloid type 1 (TRPV1) has also been reported to play a role in CNS disorders. Thus, activation of both targets, CB2 and TRPV1, offers a promising polypharmacological strategy for the treatment of neurological events including analgesia and neuroprotection. This brief research report aims to identify chemotypes with a potential dual CB2/TRPV1 profile. For this purpose, we have rationalized key structural features for activation and performed virtual screening at both targets using curated chemical libraries.

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“…In this regard, the recent finding that CBD has a profile consistent with a negative modulation of CB1R signaling both at a cellular and nuclear level ( Laprairie et al, 2015 ) offers a significant and welcome insight. Interestingly both AEA and CBD act as direct agonists of TRPV1 (and TRPV2) channels ( Bisogno et al, 2001 ; Muller et al, 2021 ); TRPV1, in particular, is ideally located in the hippocampal CA1 region to modulate excitatory glutamate signaling. Intriguingly upon the following exposure, CBD rapidly desensitizes the TRPV1 channel ( Anderson et al, 2022 ) and, thus, may reduce neuronal hyperexcitation ( Chávez et al, 2010 ; Etemad et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

CBD enhances the cognitive score of adolescent rats prenatally exposed to THC and fine-tunes relevant effectors of hippocampal plasticity

Castelli,

Lavanco,

D’Amico

et al. 2023

Front. Pharmacol.

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Introduction: An altered neurodevelopmental trajectory associated with prenatal exposure to ∆-9-tetrahydrocannabinol (THC) leads to aberrant cognitive processing through a perturbation in the effectors of hippocampal plasticity in the juvenile offspring. As adolescence presents a unique window of opportunity for “brain reprogramming”, we aimed at assessing the role of the non-psychoactive phytocannabinoid cannabidiol (CBD) as a rescue strategy to temper prenatal THC-induced harm.Methods: To this aim, Wistar rats prenatally exposed to THC (2 mg/kg s.c.) or vehicle (gestational days 5–20) were tested for specific indexes of spatial and configural memory in the reinforcement-motivated Can test and in the aversion-driven Barnes maze test during adolescence. Markers of hippocampal excitatory plasticity and endocannabinoid signaling—NMDAR subunits NR1 and 2A-, mGluR5-, and their respective scaffold proteins PSD95- and Homer 1-; CB1R- and the neuromodulatory protein HINT1 mRNA levels were evaluated. CBD (40 mg/kg i.p.) was administered to the adolescent offspring before the cognitive tasks.Results: The present results show that prenatal THC impairs hippocampal memory functions and the underlying synaptic plasticity; CBD is able to mitigate cognitive impairment in both reinforcement- and aversion-related tasks and the neuroadaptation of hippocampal excitatory synapses and CB1R-related signaling.Discussion: While this research shows CBD potential in dampening prenatal THC-induced consequences, we point out the urgency to curb cannabis use during pregnancy in order to avoid detrimental bio-behavioral outcomes in the offspring.

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TRPV1 Activation by Anandamide via a Unique Lipid Pathway

Cited by 8 publications

References 22 publications

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

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

Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators

CBD enhances the cognitive score of adolescent rats prenatally exposed to THC and fine-tunes relevant effectors of hippocampal plasticity

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