Cannabinoids and PPARα signalling

2006 ◽  
Vol 34 (6) ◽  
pp. 1095-1097 ◽  
Author(s):  
Y. Sun ◽  
S.P.H. Alexander ◽  
D.A. Kendall ◽  
A.J. Bennett
Keyword(s):  
Transcription Factor ◽  
Cannabinoid Receptor ◽  
Therapeutic Agents ◽  
Peroxisome Proliferator ◽  
Cannabinoid Receptor 1 ◽  
Cb1 Cannabinoid Receptor ◽  
Intracellular Target ◽  
Neuroprotective Treatment ◽  
Peroxisome Proliferator Activated Receptors ◽  
G Protein Coupled

Cannabinoids have been shown to possess anti-inflammatory and neuroprotective properties, which were proposed to occur mainly via activation of the G-protein-coupled receptor CB1 (cannabinoid receptor 1). Recently, certain cannabinoids have been reported to be ligands for members of the nuclear receptor transcription factor superfamily known as PPARs (peroxisome-proliferator-activated receptors). This review summarizes the evidence for cannabinoid activation of PPARs and identifies a new intracellular target for cannabinoids as therapeutic agents for neuroprotective treatment.

scholarly journals Cannabinoids: A New Group of Agonists of PPARs

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-7 ◽  
Author(s):  
Yan Sun ◽  
Andy Bennett
Keyword(s):  
Cannabinoid Receptor ◽  
Peroxisome Proliferator ◽  
Cannabinoid Receptor 1 ◽  
Nuclear Receptor Superfamily ◽  
Psychotropic Effects ◽  
Inflammatory Drugs ◽  
Peroxisome Proliferator Activated Receptors ◽  
New Compounds ◽  
G Protein Coupled ◽  
Recreational Use

Cannabinoids have been used medicinally and recreationally for thousands of years and their effects were proposed to occur mainly via activation of the G-protein-coupled receptorCB1/CB2(cannabinoid receptor 1/2). Discovery of potent synthetic analogs of the natural cannabinoids as clinically useful drugs is the sustained aim of cannabinoid research. This demands that these new compounds be free of the psychotropic effects that connected with the recreational use of cannabinoids. In preclinical studies cannabinoids displayed many of the characteristics of nonsteroidal anti-inflammatory drugs (NSAIDs) and it seems to be free of unwanted side effects. An increasing number of therapeutic actions of cannabinoid are being reported that do not appear to be mediated by eitherCB1orCB2, and recently nuclear receptor superfamily PPARs (peroxisome-proliferator-activated receptors) have been suggested as the target of certain cannabinoids. This review summarizes the evidence for cannabinoid activation on PPARs and possible associated remedial potentials.

scholarly journals G protein-coupled receptor GPR55 promotes colorectal cancer and has opposing effects to cannabinoid receptor 1

2017 ◽  
Vol 142 (1) ◽  
pp. 121-132 ◽  
Author(s):  
Carina Hasenoehrl ◽  
David Feuersinger ◽  
Eva M Sturm ◽  
Thomas Bärnthaler ◽  
Ellen Heitzer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
G Protein ◽  
Cannabinoid Receptor ◽  
G Protein Coupled Receptor ◽  
Cannabinoid Receptor 1 ◽  
Opposing Effects ◽  
G Protein Coupled

scholarly journals The Spicy Story of Cannabimimetic Indoles

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6190
Author(s):  
Allyn C. Howlett ◽  
Brian F. Thomas ◽  
John W. Huffman
Keyword(s):  
Electrostatic Interactions ◽  
Cannabinoid Receptor ◽  
Binding Pocket ◽  
Herbal Products ◽  
The Public ◽  
Aromatic Stacking ◽  
Cb1 Cannabinoid Receptor ◽  
Colchicine Binding Site ◽  
Consumer Safety ◽  
G Protein Coupled

The Sterling Research Group identified pravadoline as an aminoalkylindole (AAI) non-steroidal anti-inflammatory pain reliever. As drug design progressed, the ability of AAI analogs to block prostaglandin synthesis diminished, and antinociceptive activity was found to result from action at the CB1 cannabinoid receptor, a G-protein-coupled receptor (GPCR) abundant in the brain. Several laboratories applied computational chemistry methods to ultimately conclude that AAI and cannabinoid ligands could overlap within a common binding pocket but that WIN55212-2 primarily utilized steric interactions via aromatic stacking, whereas cannabinoid ligands required some electrostatic interactions, particularly involving the CB1 helix-3 lysine. The Huffman laboratory identified strategies to establish CB2 receptor selectivity among cannabimimetic indoles to avoid their CB1-related adverse effects, thereby stimulating preclinical studies to explore their use as anti-hyperalgesic and anti-allodynic pharmacotherapies. Some AAI analogs activate novel GPCRs referred to as “Alkyl Indole” receptors, and some AAI analogs act at the colchicine-binding site on microtubules. The AAI compounds having the greatest potency to interact with the CB1 receptor have found their way into the market as “Spice” or “K2”. The sale of these alleged “herbal products” evades FDA consumer protections for proper labeling and safety as a medicine, as well as DEA scheduling as compounds having no currently accepted medical use and a high potential for abuse. The distribution to the public of potent alkyl indole synthetic cannabimimetic chemicals without regard for consumer safety contrasts with the adherence to regulatory requirements for demonstration of safety that are routinely observed by ethical pharmaceutical companies that market medicines.

scholarly journals Organized cannabinoid receptor distribution in neurons revealed by super-resolution fluorescence imaging

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hui Li ◽  
Jie Yang ◽  
Cuiping Tian ◽  
Min Diao ◽  
Quan Wang ◽  
...  
Keyword(s):  
G Protein ◽  
Fluorescence Imaging ◽  
Cannabinoid Receptor ◽  
Super Resolution ◽  
G Protein Coupled Receptors ◽  
Cellular Functions ◽  
Cannabinoid Receptor 1 ◽  
Intracellular Organization ◽  
Dynamic Movement ◽  
G Protein Coupled

Abstract G-protein-coupled receptors (GPCRs) play important roles in cellular functions. However, their intracellular organization is largely unknown. Through investigation of the cannabinoid receptor 1 (CB1), we discovered periodically repeating clusters of CB1 hotspots within the axons of neurons. We observed these CB1 hotspots interact with the membrane-associated periodic skeleton (MPS) forming a complex crucial in the regulation of CB1 signaling. Furthermore, we found that CB1 hotspot periodicity increased upon CB1 agonist application, and these activated CB1 displayed less dynamic movement compared to non-activated CB1. Our results suggest that CB1 forms periodic hotspots organized by the MPS as a mechanism to increase signaling efficacy upon activation.

scholarly journals Effects of PPARγLigands on Leukemia

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Yoko Tabe ◽  
Marina Konopleva ◽  
Michael Andreeff ◽  
Akimichi Ohsaka
Keyword(s):  
Hematological Malignancies ◽  
Therapeutic Agents ◽  
Retinoic Acid Receptors ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Growth And Survival ◽  
Hematopoietic Malignancies ◽  
Retinoid Metabolism ◽  
Natural Ligands ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) and retinoic acid receptors (RARs), members of the nuclear receptor superfamily, are transcription factors that regulate a variety of important cellular functions. PPARs form heterodimers retinoid X receptor (RXR), an obligate heterodimeric partner for other nuclear receptors. Several novel links between retinoid metabolism and PPAR responses have been identified, and activation of PPAR/RXR expression has been shown to increase response to retinoids. PPARγhas emerged as a key regulator of cell growth and survival, whose activity is modulated by a number of synthetic and natural ligands. While clinical trials in cancer patients with thiazolidinediones (TZD) have been disappointing, novel structurally different PPARγligands, including triterpenoids, have entered clinical arena as therapeutic agents for epithelial and hematopoietic malignancies. Here we shall review the antitumor advances of PPARγ, alone and in combination with RARαligands in control of cell proliferation, differentiation, and apoptosis and their potential therapeutic applications in hematological malignancies.

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