August 2022 In vitro assays for the functional characterization of (psychedelic) substances at the serotonin are substances that induce alterations in mood, perception, and thought, and have the activation of serotonin the source #DrGPCR #GPCR #IndustryNews 5-HT2AR, GPCR, hallucinogens, in vitro assay, psychedelics; serotonin

Microscopy, authors reported the structures of four protein complexes integrated by a complete human serotonin Prior to this report we did not know how different serotonin receptor subtypes which share high sequence The binding pockets for serotonin were virtually identical between the receptor-Gs and receptor-Gi complexes Therefore the authors propose that the relative lengths of TM5 and TM6 in serotonin receptors function These findings contribute to progress in understanding how serotonin receptors, one of the largest subfamilies

Serotonin1A receptors are important members of the GPCR family and are implicated in neuropsychiatric cholesterol in lateral dynamics of GPCRs, we utilized single particle tracking (SPT) to monitor diffusion of serotonin1A

The 5HT2C serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms

September 2022 "Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute

between neurotrophic factor-α1 (NF-α1/carboxypeptidase E, CPE) and human 5-HTR1E, a G protein-coupled serotonin interacts with 5-HTR1E via 3 salt bridges, stabilized by several hydrogen bonds, independent of the serotonin Thus, NF-α1/CPE uniquely interacts with serotonin receptor 5-HTR1E to activate the β-arrestin/ERK/CREB

August 2022 GPCRs steer G i and G s selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors "Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates Here, we report the structures of the serotonin receptors 5-HT4, 5-HT6, and 5-HT7 with Gs, and 5-HT4 coupling selectivity or promiscuity by class A GPCRs and extend the basis of ligand recognition at serotonin

August 2022 "A confluence of factors has renewed interest in the scientific understanding and translational potential of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin: the desire for additional approaches to mental health care, incremental progress in basic and clinical research, and the reconsideration and relaxation of existing drug policies. With the United States Food and Drug Administration's designation of psilocybin as a "Breakthrough Therapy" for treatment-resistant depression, a new path has been forged for the conveyance of psychedelics to the clinic. Essential to the further development of such applications, however, is a clearer understanding of how these drugs exert their effects at the molecular level. Here we review the current knowledge regarding the molecular details of psychedelic drug actions and suggest that these discoveries can facilitate new insights into their hallucinogenic and therapeutic mechanisms." Read more at the source #DrGPCR #GPCR #IndustryNews

Considering the central role of the serotonin 5-HT2A receptor in the distinct effects of psychedelics

Lysophosphatidic Acid and Several Neurotransmitters Converge on Rho-Kinase 2 Signaling to Manage Motoneuron Excitability Intrinsic membrane excitability (IME) sets up neuronal responsiveness to synaptic drive. Several neurotransmitters and neuromodulators, acting through G-protein-coupled receptors (GPCRs), fine-tune motoneuron (MN) IME by modulating background K+ channels TASK1. However, intracellular partners linking GPCRs to TASK1 modulation are not yet well-known. We hypothesized that isoform 2 of rho-kinase (ROCK2), acting as downstream GPCRs, mediates adjustment of MN IME via TASK1. Electrophysiological recordings were performed in hypoglossal MNs (HMNs) obtained from adult and neonatal rats, neonatal knockout mice for TASK1 ( task1 -/-) and TASK3 ( task3 -/-, the another highly expressed TASK subunit in MNs), and primary cultures of embryonic spinal cord MNs (SMNs). Small-interfering RNA (siRNA) technology was also used to knockdown either ROCK1 or ROCK2. Furthermore, ROCK activity assays were performed to evaluate the ability of various physiological GPCR ligands to stimulate ROCK. Microiontophoretically applied H1152, a ROCK inhibitor, and siRNA-induced ROCK2 knockdown both depressed AMPAergic, inspiratory-related discharge activity of adult HMNs in vivo , which mainly express the ROCK2 isoform. In brainstem slices, intracellular constitutively active ROCK2 (aROCK2) led to H1152-sensitive HMN hyper-excitability. The aROCK2 inhibited pH-sensitive and TASK1-mediated currents in SMNs. Conclusively, aROCK2 increased IME in task3 -/-, but not in task1 -/- HMNs. MN IME was also augmented by the physiological neuromodulator lysophosphatidic acid (LPA) through a mechanism entailing Gαi/o-protein stimulation, ROCK2, but not ROCK1, activity and TASK1 inhibition. Finally, two neurotransmitters, TRH, and 5-HT, which are both known to increase MN IME by TASK1 inhibition, stimulated ROCK2, and depressed background resting currents via Gαq/ROCK2 signaling. These outcomes suggest that LPA and several neurotransmitters impact MN IME via Gαi/o/Gαq-protein-coupled receptors, downstream ROCK2 activation, and subsequent inhibition of TASK1 channels. Read full article

hallucinogens, affect processes related to perception, cognition and sensory processing mostly via the serotonin

101 in the CRAC Motif in Transmembrane Helix 2 Confers Cholesterol-Induced Thermal Stability to the Serotonin The serotonin1A receptor is a crucial neurotransmitter receptor in the GPCR family involved in a multitude In addition, we showed that membrane cholesterol stabilizes the serotonin1A receptor against thermal In the present work, we explored the molecular basis of cholesterol-induced thermal stability of the serotonin1A Our results show that a mutation in the K101 residue leads to loss in thermal stability of the serotonin1A

October 2022 Cholesterol-Dependent Dynamics of the Serotonin1A Receptor Utilizing Single Particle Tracking Serotonin1A receptors are important members of the GPCR family and are implicated in neuropsychiatric cholesterol in lateral dynamics of GPCRs, we utilized single particle tracking (SPT) to monitor diffusion of serotonin1A

Neuroscience Photoactivatable Agonist-Antagonist Pair as a Tool for Precise Spatiotemporal Control of Serotonin strategy for hit identification Reviews, GPCRs, and more The discovery, structure, and function of 5-HTR1E serotonin

Kossatz, Michel Bouvier, Jana Selent, et al. for their study on G protein-specific mechanisms in the serotonin Epithelial Proliferation, Migration, and Cellular Respiration G protein-specific mechanisms in the serotonin

G-protein-coupled receptors (GPCRs) such as dopamine D1R, D2LR, D3R, and D4R, vasopressin V1AR, and serotonin

Structural and Molecular Insights into GPCR Function Synergistic and Competitive Lipid Interactions in the Serotonin

GHSR1a heterodimerises with multiple G protein-coupled receptors (GPCRs), including dopamine D1 and D2, serotonin

prospectively docked ultra-large libraries of molecules against unrefined AF2 models of the σ2 and 5-HT2A serotonin

and Taste Ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-HT (serotonin

/ calcitonin receptor signaling suppresses feeding and weight gain in female rats Neuropeptide and serotonin receptor targeting by a nanobody antagonist Probing the energy landscape of the lipid interactions of the serotonin1A

interception Structural and Molecular Insights into GPCR Function Structural bioinformatics studies of serotonin

Serotonin 5-HT7 receptor slows down the Gs protein: a single molecule perspective.

Characterization of serotonin-5-HTR1E signaling pathways and its role in cell survival.

Methods & Updates in GPCR Research Improved green and red GRAB sensors for monitoring spatiotemporal serotonin

predicted mouse melanopsins with blue spectral shifts deliver efficient subcellular signaling Striatal serotonin

dopamine neurons and dopamine release in the nucleus accumbens Understanding the Molecular Regulation of Serotonin

Evidence that RXFP4 is located in enterochromaffin cells and can regulate production and release of serotonin