Marijuana has been used for thousands of years to affect human health. Dissecting the peripheral effects from the central psychotropic effects has revealed a complex interplay between cannabinoids, endocannabinoids and their receptors. This review examines recent advances in understanding the expression, regulation and utilization of the CB(2) receptor. Here we highlight the molecular aspects of the CB(2) receptor, CB(2) receptor signaling and new ligands for this receptor. We focus in the rest of the review on recent findings in the immune system, the gastrointestinal tract and liver, the brain and the cardiovascular system and airways as examples of areas where new developments in our understanding of the CB(2) receptor have occurred. Early studies focused on expression of this receptor under baseline physiologic conditions; however, perturbations such as those that occur during inflammation, ischemia/reperfusion injury and cancer are revealing a critical role for the CB(2) receptor in regulating these disease processes amongst others. As a result, the CB(2) receptor is an appealing therapeutic target as well as a useful tool for shedding new light on physiological regulatory processes throughout the body.
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http://dx.doi.org/10.2174/092986710790980041 | DOI Listing |
Nat Commun
January 2025
IGF, Université de Montpellier, CNRS, INSERM, 34094, Montpellier, France.
The metabotropic glutamate receptors (mGlus) are class C G protein-coupled receptors (GPCR) that form obligate dimers activated by the major excitatory neurotransmitter L-glutamate. The architecture of mGlu receptor comprises an extracellular Venus-Fly Trap domain (VFT) connected to the transmembrane domain (7TM) through a Cysteine-Rich Domain (CRD). The binding of L-glutamate in the VFTs and subsequent conformational change results in the signal being transmitted to the 7TM inducing G protein binding and activation.
View Article and Find Full Text PDFMed
January 2025
Cambridge University Hospital NHS Trust, Hills Road, Cambridge CB2 2QQ, UK. Electronic address:
The ALIGN trial demonstrates that atrasentan, an endothelin A (ETA) receptor antagonist, reduces proteinuria in patients with IgA nephropathy (IgAN), a key goal to slow progressive renal disease. These results are consistent with those from sparsentan, a combined ETA and angiotensin inhibitor, in IgAN, suggesting two-year data will show atrasentan improves renal outcomes.
View Article and Find Full Text PDFNutrients
December 2024
Department of Nephrocardiology, Medical University of Lodz, 90-549 Lodz, Poland.
This narrative review explores the benefits and risks of cannabinoids in kidney health, particularly in individuals with pre-existing renal conditions. It discusses the roles of cannabinoid receptor ligands (phytocannabinoids, synthetic cannabinoids, and endocannabinoids) in kidney physiology. The metabolism and excretion of these substances are also highlighted, with partial elimination occurring via the kidneys.
View Article and Find Full Text PDFEur J Pharmacol
January 2025
Laboratory of Pharmacology of Pain, Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
Neuropathy is the most common complication of diabetes, leading to painful symptoms like hyperalgesia. Current treatments for diabetic painful neuropathy often prove inadequate, necessitating the exploration of new pharmacological approaches. Therefore, this study aimed to investigate the potential antinociceptive effect of aspirin-triggered lipoxin A4 (ATL), a specialized pro-resolving lipid mediator, when administered alone or in combination with cannabinoid agonists, to alleviate diabetic neuropathic pain.
View Article and Find Full Text PDFCells
December 2024
Centre for Health and Life Sciences, Coventry University, Coventry CV1 5FB, UK.
The adenosine A1 receptor (AR) is a promising target for pain treatment. However, the development of therapeutic agonists is hampered by adverse effects, mainly including sedation, bradycardia, hypotension, or respiratory depression. Recently discovered molecules able to overcome this impediment are the positive allosteric modulator MIPS521 and the A1R-selective agonist BnOCPA, which are both potent and powerful analgesics with fewer side effects.
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