A5053915349- Cannabis and Cannabinoid Research
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Pancreatic function and diabetes
- Pharmacological Receptor Mechanisms and Effects
- Neurotransmitter Receptor Influence on Behavior
- Tryptophan and brain disorders
- Forensic Toxicology and Drug Analysis
- Enzyme Structure and Function
- Electrolyte and hormonal disorders
- Cancer, Stress, Anesthesia, and Immune Response
- Regulation of Appetite and Obesity
- Amyotrophic Lateral Sclerosis Research
- Intracerebral and Subarachnoid Hemorrhage Research
- Biochemical Analysis and Sensing Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Cerebrospinal fluid and hydrocephalus
- melanin and skin pigmentation
- Neuropeptides and Animal Physiology
- Poisoning and overdose treatments
- Nicotinic Acetylcholine Receptors Study
- Immune Cell Function and Interaction
- Sleep and Wakefulness Research
- Diet, Metabolism, and Disease
- Biotin and Related Studies
University of Auckland
2015-2024
Maurice Wilkins Centre
2021-2024
University of Newcastle Australia
2021
Communities In Schools of Orange County
2016
Biased agonism at G protein-coupled receptors describes the phenomenon whereby some drugs can activate downstream signaling activities to relative exclusion of others. Descriptions biased focusing on differential engagement proteins versus β-arrestins are commonly limited by small response windows obtained in pathways that not amplified or less effectively coupled receptor engagement, such as β-arrestin recruitment. At μ-opioid (MOR), protein-biased ligands have been proposed induce...
The cannabinoid receptor type 1 (CB1 ) has an allosteric binding site. drugs ORG27569 {5-chloro-3-ethyl-N-[2-[4-(1-piperidinyl)phenyl]ethyl]-1H-indole-2-carboxamide} and PSNCBAM-1 {1-(4-chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea} have been extensively characterized with regard to their effects on signalling of the orthosteric ligand CP55,940 {(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol}, studies suggested that these modulators...
Background and Purpose CB 1 receptor signalling is canonically mediated through inhibitory Gα i proteins, but occurs other G proteins under some circumstances, s being the most characterized secondary pathway. Determinants of this switch identified to date include blockade, /D 2 co‐stimulation, agonist class cell background. Hence, we examined effects number different ligands on signalling. Experimental Approach receptors were expressed in HEK cells at levels, for cAMP by real‐time BRET...
Arrestin translocation and signaling have come to the fore of G protein-coupled receptor molecular pharmacology field. Some receptor-arrestin interactions are relatively well understood considered responsible for specific therapeutic or adverse outcomes. Coupling arrestins with cannabinoid receptors 1 (CB1) 2 (CB2) has been reported, though majority studies not systematically characterized differential ligand dependence this activity. In addition, many prior utilized bovine (rather than...
Cannabinoid receptor 2 (CB2) is a promising therapeutic target for immunological modulation. There is, however, deficit of knowledge regarding CB2 signaling and function in human primary immunocompetent cells. We applied an experimental paradigm which closely models the situ state leukocytes (PBMC; peripheral blood mononuclear cells) to characterize activation number pathways response CB2-selective ligand (HU308). observed "lag" phase unchanged cAMP concentration prior development...
The orphan receptor GPR18 has become a research target following the discovery of putative endogenous agonist, N-arachidonoyl glycine (NAGly). Chemical similarity between NAGly and endocannabinoid anandamide suggested hypothesis that is third cannabinoid receptor. GPR18-mediated cellular signalling through inhibition cyclic adenosine monophosphate (cAMP) phosphorylation extracellular signal-regulated kinase (ERK), in addition to physiological consequences such as regulation migration...
Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment numerous conditions, including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite significance this receptor, researchers lack reliable tools to address questions concerning expression complex mechanism CB2R signaling, especially in cell-type tissue-dependent contexts. Herein, we report first time a versatile ligand platform modular design collection highly specific...
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. The pattern neuron loss along the spinal cord follows deposition phosphorylated TDP-43 aggregates. blood-spinal barrier (BSCB) restricts entry into parenchyma blood components that can promote degeneration, but in ALS there evidence for breakdown. Here we sought to quantify BSCB breakdown axis, determine whether displays same patterning as...
Cannabinoid Receptor 2 (CB2) is a promising therapeutic target for modulating inflammation. Canonical signalling responses to receptor ligands are critically dependent on cell surface expression. However, it also now appreciated that intracellular G protein-coupled receptors can contribute and influence functional outcomes. Therefore, understanding how the subcellular distribution of controlled highly pertinent. CB2 observed be expressed at as well having considerable proportion...
Cannabinoid type 2 receptor (CB2R) is an attractive target for the treatment of pain and inflammatory disorders. Availability a selective CB2R fluorescent ligand to study expression localization in healthy disease conditions would greatly contribute improving our understanding this receptor. Herein, we report series chromenopyrazole-based ligands. The highest affinity was Cy5-containing 24 (hCB2R pKi = 7.38 ± 0.05), which had 131-fold selectivity over CB1R. In cAMP BRET assay, behaved as...
N-arachidonyl dopamine (NADA) has been identified as a putative endocannabinoid, but there is little information about which signalling pathways it activates. The purpose of this study was to identify the activated by NADA in vitro.
Cannabinoid Receptor 2 (CB2) is predominantly distributed in immune tissues and cells a promising therapeutic target for modulating inflammation. In this study we designed synthesised series of 2,4,6-trisubstituted 1,3,5-triazines with piperazinyl-alkyl or 1,2-diethoxyethane (PEG2) chains as CB2 agonists, all which were predicted to be considerably more polar than typical cannabinoid ligands. series, found that triazines containing an adamantanyl group conducive binding whereas those...
1. Receptor transport between intracellular compartments has important consequences for receptor function and is an exciting area of current study. Existing methods studying trafficking often require labour-intensive techniques or are difficult to quantify reliably. We report a novel high-throughput method that uses automated imaging analysis tools accurately cannabinoid CB1 trafficking. 2. Haemagglutinin (HA)-tagged was stably expressed in HEK-293 cells cell surface total receptors were...
High affinity, cannabinoid type 2 receptor selective ligand.