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

Paul Insel About this episode In 1975, Dr. Paul Insel was at the FASEB experimental biology meeting in Atlantic City. From that point on, Paul was hooked and has since studied receptor function in human physiology, receptor Today, Paul and his team focus on previously unrecognized receptors with the hopes to use these as novel Paul Insel on the web Insel Laboratory Institute of Engineering in Medicine UC San Diego UCSD Profiles

Paul Insel About this episode Dr. Paul Insel is currently a Distinguished Professor of Pharmacology and the University of California San Paul thinks broadly about science and has been actively publishing papers about his ideas on how COVID Paul Insel on the web Insel Laboratory Institute of Engineering in Medicine UC San Diego UCSD Profiles

Paul Clarck , where she studied opioid receptors.