scholarly journals Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses

2021 ◽  
Vol 12 ◽  
Author(s):  
Kenneth B. Walsh ◽  
Amanda E. McKinney ◽  
Andrea E. Holmes
Keyword(s):  
Transient Receptor Potential ◽  
Cannabis Sativa ◽  
Trp Channels ◽  
Current Knowledge ◽  
Synergistic Activity ◽  
Molecular Pharmacology ◽  
Isolation And Characterization ◽  
Therapeutic Uses ◽  
Cb2 Receptors ◽  
Cb1 And Cb2 Receptors

The medicinal use of Cannabis sativa L. can be traced back thousands of years to ancient China and Egypt. While marijuana has recently shown promise in managing chronic pain and nausea, scientific investigation of cannabis has been restricted due its classification as a schedule 1 controlled substance. A major breakthrough in understanding the pharmacology of cannabis came with the isolation and characterization of the phytocannabinoids trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This was followed by the cloning of the cannabinoid CB1 and CB2 receptors in the 1990s and the subsequent discovery of the endocannabinoid system. In addition to the major phytocannabinoids, Δ9-THC and CBD, cannabis produces over 120 other cannabinoids that are referred to as minor and/or rare cannabinoids. These cannabinoids are produced in smaller amounts in the plant and are derived along with Δ9-THC and CBD from the parent cannabinoid cannabigerolic acid (CBGA). While our current knowledge of minor cannabinoid pharmacology is incomplete, studies demonstrate that they act as agonists and antagonists at multiple targets including CB1 and CB2 receptors, transient receptor potential (TRP) channels, peroxisome proliferator-activated receptors (PPARs), serotonin 5-HT1a receptors and others. The resulting activation of multiple cell signaling pathways, combined with their putative synergistic activity, provides a mechanistic basis for their therapeutic actions. Initial clinical reports suggest that these cannabinoids may have potential benefits in the treatment of neuropathic pain, neurodegenerative diseases, epilepsy, cancer and skin disorders. This review focuses on the molecular pharmacology of the minor cannabinoids and highlights some important therapeutic uses of the compounds.

scholarly journals Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

2021 ◽  
Vol 22 (2) ◽  
pp. 778
Author(s):  
Anna Stasiłowicz ◽  
Anna Tomala ◽  
Irma Podolak ◽  
Judyta Cielecka-Piontek
Keyword(s):  
Pharmacological Activity ◽  
Transient Receptor Potential ◽  
Cannabis Sativa ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Raw Material ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood–brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.

scholarly journals TRP Channels as Drug Targets to Relieve Itch

2018 ◽  
Vol 11 (4) ◽  
pp. 100 ◽  
Author(s):  
Zili Xie ◽  
Hongzhen Hu
Keyword(s):  
Drug Targets ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Protective Role ◽  
Chronic Itch ◽  
Transient Receptor

Although acute itch has a protective role by removing irritants to avoid further damage, chronic itch is debilitating, significantly impacting quality of life. Over the past two decades, a considerable amount of stimulating research has been carried out to delineate mechanisms of itch at the molecular, cellular, and circuit levels. There is growing evidence that transient receptor potential (TRP) channels play important roles in itch signaling. The purpose of this review is to summarize our current knowledge about the role of TRP channels in the generation of itch under both physiological and pathological conditions, thereby identifying them as potential drug targets for effective anti-itch therapies.

scholarly journals Molecular mechanism of TRPV2 channel modulation by cannabidiol

2019 ◽  
Author(s):  
Ruth A. Pumroy ◽  
Amrita Samanta ◽  
Yuhang Liu ◽  
Taylor E.T. Hughes ◽  
Siyuan Zhao ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Cannabis Sativa ◽  
Trp Channels ◽  
Critical Role ◽  
Channel Gating ◽  
Receptor Potential ◽  
Lipid Binding ◽  
Transient Receptor Potential Vanilloid ◽  
Structure Based Drug Design ◽  
Transient Receptor

SUMMARYTransient receptor potential vanilloid 2 (TRPV2) plays a critical role in neuronal development, cardiac function, immunity, and cancer. Cannabidiol (CBD), the non-psychotropic therapeutically active ingredient of Cannabis sativa, is a potent activator of TRPV2 and also modulates other transient receptor potential (TRP) channels. Here, we determined structures of the full-length TRPV2 channel in a CBD-bound state in detergent and in PI(4,5)P2 enriched nanodiscs by cryo-electron microscopy. CBD interacts with TRPV2 through a hydrophobic pocket located between S5 and S6 helices of adjacent subunits, which differs from known ligand and lipid binding sites in other TRP channels. Comparison between apo- and two CBD-bound TRPV2 structures reveals that the S4-S5 linker plays a critical role in channel gating upon CBD binding. The TRPV2 “vanilloid” pocket, which is critical for ligand-dependent gating in other TRPV channels, stays unoccupied by annular lipids, PI(4,5)P2, or CBD. Together these results provide a foundation to further understand TRPV channel gating properties and their divergent physiological functions and to accelerate structure-based drug design.

scholarly journals Role of TRP channels in the cardiovascular system

2015 ◽  
Vol 308 (3) ◽  
pp. H157-H182 ◽  
Author(s):  
Zhichao Yue ◽  
Jia Xie ◽  
Albert S. Yu ◽  
Jonathan Stock ◽  
Jianyang Du ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Mechanical Stretch ◽  
Signal Pathways ◽  
Variable Degree ◽  
Cell Functions

The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca2+-permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca2+ entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases.

scholarly journals Molecular mechanism of TRPV2 channel modulation by cannabidiol

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ruth A Pumroy ◽  
Amrita Samanta ◽  
Yuhang Liu ◽  
Taylor ET Hughes ◽  
Siyuan Zhao ◽  
...  
Keyword(s):  
Bound States ◽  
Transient Receptor Potential ◽  
Cannabis Sativa ◽  
Trp Channels ◽  
Critical Role ◽  
Channel Gating ◽  
Receptor Potential ◽  
Lipid Binding ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

Transient receptor potential vanilloid 2 (TRPV2) plays a critical role in neuronal development, cardiac function, immunity, and cancer. Cannabidiol (CBD), the non-psychotropic therapeutically active ingredient of Cannabis sativa, is an activator of TRPV2 and also modulates other transient receptor potential (TRP) channels. Here, we determined structures of the full-length rat TRPV2 channel in apo and CBD-bound states in nanodiscs by cryo-electron microscopy. We show that CBD interacts with TRPV2 through a hydrophobic pocket located between S5 and S6 helices of adjacent subunits, which differs from known ligand and lipid binding sites in other TRP channels. CBD-bound TRPV2 structures revealed that the S4-S5 linker plays a critical role in channel gating upon CBD binding. Additionally, nanodiscs permitted us to visualize two distinct TRPV2 apo states in a lipid environment. Together these results provide a foundation to further understand TRPV channel gating, their divergent physiological functions, and to accelerate structure-based drug design.

Assembly domains in TRP channels

2007 ◽  
Vol 35 (1) ◽  
pp. 84-85 ◽  
Author(s):  
R. Schindl ◽  
C. Romanin
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Large Family ◽  
Receptor Potential ◽  
Trp Channel ◽  
Channel Formation ◽  
Transient Receptor ◽  
Sensory Functions

The large family of mammalian TRP (transient receptor potential) ion channels encompasses diverse sensory functions. TRP proteins consist of six transmembrane domains, with a pore–loop motif between the fifth and sixth domains and cytosolic N- and C-termini. The intracellular strands not only interact with various proteins and lipids, but also include essential multimerization regions. This review summarizes the current knowledge of the intrinsic assembly domains that assure tetrameric TRP channel formation.

scholarly journals TRP Channels in Human Prostate

2010 ◽  
Vol 10 ◽  
pp. 1597-1611 ◽  
Author(s):  
Carl Van Haute ◽  
Dirk De Ridder ◽  
Bernd Nilius
Keyword(s):  
Prostate Cancer ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Human Prostate ◽  
Prostate Carcinogenesis ◽  
Potential Impact ◽  
Transient Receptor ◽  
Prostate Diseases

This review gives an overview of morphological and functional characteristics in the human prostate. It will focus on the current knowledge about transient receptor potential (TRP) channels expressed in the human prostate, and their putative role in normal physiology and prostate carcinogenesis. Controversial data regarding the expression pattern and the potential impact of TRP channels in prostate function, and their involvement in prostate cancer and other prostate diseases, will be discussed.

scholarly journals TRP Channels as Sensors of Chemically-Induced Changes in Cell Membrane Mechanical Properties

2019 ◽  
Vol 20 (2) ◽  
pp. 371 ◽  
Author(s):  
Justyna Startek ◽  
Brett Boonen ◽  
Karel Talavera ◽  
Victor Meseguer
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Membrane Properties ◽  
Chemically Induced ◽  
Bacterial Endotoxins ◽  
Highly Sensitive ◽  
Transient Receptor ◽  
Induced Changes

Transient Receptor Potential ion channels (TRPs) have been described as polymodal sensors, being responsible for transducing a wide variety of stimuli, and being involved in sensory functions such as chemosensation, thermosensation, mechanosensation, and photosensation. Mechanical and chemical stresses exerted on the membrane can be transduced by specialized proteins into meaningful intracellular biochemical signaling, resulting in physiological changes. Of particular interest are compounds that can change the local physical properties of the membrane, thereby affecting nearby proteins, such as TRP channels, which are highly sensitive to the membrane environment. In this review, we provide an overview of the current knowledge of TRP channel activation as a result of changes in the membrane properties induced by amphipathic structural lipidic components such as cholesterol and diacylglycerol, and by exogenous amphipathic bacterial endotoxins.

scholarly journals TRPC Channels: Dysregulation and Ca2+ Mishandling in Ischemic Heart Disease

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 173 ◽  
Author(s):  
Débora Falcón ◽  
Isabel Galeano-Otero ◽  
Marta Martín-Bórnez ◽  
María Fernández-Velasco ◽  
Isabel Gallardo-Castillo ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Experimental Models ◽  
Cardiac Cells ◽  
Membrane Receptors ◽  
Trpc Channels ◽  
Ischemia And Reperfusion

Transient receptor potential canonical (TRPC) channels are ubiquitously expressed in excitable and non-excitable cardiac cells where they sense and respond to a wide variety of physical and chemical stimuli. As other TRP channels, TRPC channels may form homo or heterotetrameric ion channels, and they can associate with other membrane receptors and ion channels to regulate intracellular calcium concentration. Dysfunctions of TRPC channels are involved in many types of cardiovascular diseases. Significant increase in the expression of different TRPC isoforms was observed in different animal models of heart infarcts and in vitro experimental models of ischemia and reperfusion. TRPC channel-mediated increase of the intracellular Ca2+ concentration seems to be required for the activation of the signaling pathway that plays minor roles in the healthy heart, but they are more relevant for cardiac responses to ischemia, such as the activation of different factors of transcription and cardiac hypertrophy, fibrosis, and angiogenesis. In this review, we highlight the current knowledge regarding TRPC implication in different cellular processes related to ischemia and reperfusion and to heart infarction.

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