Search Results

September 2022 "The activation of phospholipase C (PLC) is thought to have a key role in the cardiomyocyte

Here, we provide evidence that distal carboxyl-terminal tail (C-tail), but not proximal, phosphorylation site-directed mutagenesis and bioluminescence resonance energy transfer approaches that distal, not proximal, C-tail In addition, we show that GPCRs that have similarly positioned C-tail phosphoresidues are also able to However, although necessary for some GPCRs, we found that distal C-tail sites might not be sufficient In conclusion, this study provides evidence that distal C-tail phosphorylation sites specify GRK-βarrestin-mediated

October 2022 Coincident Regulation of PLCβ Signaling by Gq-Coupled and μOpioid Receptors Opposes Opioid- Mediated Antinociception "Pain management is a significant problem worldwide. The current frontline approach for pain-management is the use of opioid analgesics. The primary analgesic target of opioids is the μ-opioid receptor (MOR). Deletion of phospholipase Cβ3 (PLCβ3), or selective inhibition of Gβγ regulation of PLCβ3, enhances the potency of the antinociceptive effects of morphine suggesting a novel strategy for achieving opioid sparing effects. Here we investigated a potential mechanism for regulation of PLC signaling downstream of MOR in HEK293 cells and found that MOR alone could not stimulate PLC, but rather required a coincident signal from a Gq coupled receptor. Knockout of PLCβ3, or pharmacological inhibition of its upstream regulators, Gβγ or Gq, ex vivo in periaqueductal gray (PAG) slices increased the potency of the selective MOR agonist DAMGO in inhibiting presynaptic GABA release. Finally, inhibition of Gq-GPCR coupling in mice enhanced the antinociceptive effects of morphine. These data support a model where Gq and Gβγ-dependent signaling cooperatively regulate PLC activation to decrease MOR-dependent antinociceptive potency. Ultimately this could lead to identification of new non-MOR targets that would allow for lower dose utilization of opioid analgesics. " Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Newsletter HERE

Josh C Snyder (2012) Dr.

Josh Pottel About Dr. Josh Pottel "I lead Molecular Forecaster Inc. Josh Pottel on the web Molecular Forecaster LinkedIn BlueSky Google Scholar Twitter Dr.

Principles of Pharmacology in Drug Discovery I Techniques for Effective Lead Optimization of Candidate Molecules Dr. Terry Kenakin Techniques for Effective Lead Optimization of Candidate Molecules GPCRs have been and arguably still are the most prolific and fertile therapeutic drug targets; this course describes the essential pharmacologic techniques and knowledge required to create a GPCR Target Program aimed at the discovery of new Drugs. The course will focus on the methods used to quantify GPCR ligand activity (agonists, antagonists, modulators) and the process of characterizing the mechanism of action of ligands to enable the prediction of activity in vivo systems. In general, registrants will receive a comprehensive understanding of the unique science of pharmacology and how it can describe drug action in system-independent ways. Registrants will learn: Essentials of measuring pharmacologic activity of ligands (affinity, efficacy, co-operativity). Application of this knowledge to determine the mechanism of action of new GPCR ligands. The required elements of a comprehensive and effective GPCR Discovery. Modules: October 3rd: GPCR Project Initiation and Design for Discovery of New Molecules. October 10th: Drug Affinity: Measurement of Antagonism (Binding and Function) / Classifying Antagonists. October 17th: Agonists and Efficacy: A New World of GPCR Efficacies / Biased Signaling. October 24th: Allosteric Modulators: NAMs, PAMs, Special Properties, Methods to quantify the allosteric effect. Registrations start on Monday, July 15th, 2024. Classes will be live from Zoom on Thursdays from 10 am to 11:30 am EST. Sessions will include a 1-hour live lecture plus 30 minutes of Q&A. Participants who complete the course will get an online certification signed by the professor and the Dr.GPCR Team. A splendid time is guaranteed for all. What others are saying about the courses Dr. Hoare is very experienced in the field. What came as a pleasant surprise was how didactical and well-thought-out his course was—highly recommended. The really unexpected was that the Q&A sessions reached the highest level—beyond excellent. I am a convert! I will keep Dr. GPCR and the offered resources in my work sphere Anonymous Dr. Hoare's extensive and elaborative explanation of the topics at hand was excellent and very digestible. Thoroughly enjoyed learning from him Anonymous Thank you for bringing this course with Dr. Kenakin. I wish Dr. GPCR the best for the sake of promoting more educational opportunities that are sorely needed in the field Anonymous Dr. Kenakin is a leading expert in the field. Aside from his vast experience in drug development, not to mention his extensive publication record, Dr. Kenakin is a masterful teacher and communicator. Anonymous The content had enough depth to satisfy the hunger for theory while being full of practical knowledge Anonymous The course was very practical and easily translatable to experiments that we could do in our own labs. It was clear that Dr. Hoare is very in touch with the technical and human challenges we encounter in our work Anonymous The best pharmacology teacher teaming up with the best GPCR community platform to help train and inspire the next generation of scientists. Also super-valuable for those of us learning how to teach pharmacology Anonymous What would you like to learn today?