September 2022 "Systemic sclerosis (SSc) is a systemic autoimmune disease with the key features of inflammation

The chemokine system exhibits great versatility, with more than 50 chemokines interacting with over 20 receptor-chemokine complexes and revealing the diverse and multifaceted nature of the chemokine receptor system study of all structures of CKRs characterizes the molecular recognition processes governing the CKR system experimental structures of chemokine receptors, which provide insights into the complexity of the chemokine system

September 2022 "The endocannabinoid system plays a key role in the intersection of the nervous, endocrine , and immune systems, regulating not only their functions but also how they interplay with each other cell wall, disrupt not only the hypothalamic–pituitary–adrenal axis but also affects other endocrine systems

cells expressing the chemokine receptor endogenously together with relevant enzymes and co-receptor systems our understanding on the dynamics and biological relevance of these PTMs in the chemokine receptor system which may ultimately allow for new precise targeting of the immune system.

Although they form an ancient signaling system, there is still a great deal of variety in neuropeptides By comparison, we found that the Releasing Hormone-Related Peptides (GnRHs) system of Sternorrhyncha Additionally, we discovered that the neuropeptide signaling systems of Sternorrhyncha were very different This research provides more knowledge on neuropeptide systems and sets the groundwork for the creation

August 2022 "Host response to infection involves the activation of the complement system leading to the

GPCRs Are Optimal Regulators of Complex Biological Systems and Orchestrate the Interface between Health of the physiological balance between healthy and pathological conditions; thus, their importance in systems The molecular diversity of GPCR signaling systems is likely to be closely associated with disease-associated compartmentalization, thus enabling a nuanced GPCR-based capacity to interdict multiple disease pathomechanisms at a systemic

October 2022 "Perturbation of the endocannabinoid system can have profound effects on immune function Microglia are one of few cell types with a self-contained endocannabinoid system and are positioned at the interface between the immune system and the central nervous system. results with respect to the effects of pro-inflammatory conditions on the microglial endocannabinoid system stimuli, lipopolysaccharide and interferon gamma, on the abundance of components of the endocannabinoid system

September 2022 Dynamics of tumor-associated macrophages in a quantitative systems pharmacology model of immunotherapy in triple-negative breast cancer "Quantitative systems pharmacology (QSP) modeling is an emerging mechanistic computational approach that couples drug pharmacokinetics/pharmacodynamics and

between antagonist, partial agonist, and biased agonist outcomes in various primary and clonal cell systems

Coordinated transcriptomics and peptidomics of central nervous system identify neuropeptides and their Here, we generated a transcriptome of the central nervous system (CNS) of G. molesta.

August 2022 "The calcium-permeable cation channel TRPM3 can be activated by heat and the endogenous steroid pregnenolone sulfate. TRPM3's best understood function is its role as a peripheral noxious heat sensor in mice. However, the channel is expressed in various tissues and cell types including neurons as well as glial and epithelial cells. TRPM3 expression patterns differ between species and change during development. Furthermore, a plethora of TRPM3 variants that result from alternative splicing have been identified and the majority of these isoforms are yet to be characterized. Moreover, the mechanisms underlying regulation of TRPM3 are largely unexplored. In addition, a micro-RNA gene (miR-204) is located within the TRPM3 gene. This complexity makes it difficult to obtain a clear picture of TRPM3 characteristics. However, a clear picture is needed to unravel TRPM3's full potential as experimental tool, diagnostic marker and therapeutic target. Therefore, the newest data related to TRPM3 have to be discussed and to be put in context as soon as possible to be up-to-date and to accelerate the translation from bench to bedside. The aim of this review is to highlight recent results and developments with particular focus on findings from studies involving ocular tissues and cells or peripheral neurons of rodents and humans." Read more at the source #DrGPCR #GPCR #IndustryNews

schizophrenia-relevant brain circuits "Although the cannabinoid type-2 receptor (CB2) is highly expressed in the immune system emerging evidence points to CB2 playing a key role in regulating neuronal function in the central nervous system

September 2022 "Perception of threats is essential for survival. Previous findings suggest that parallel pathways independently relay innate threat signals from different sensory modalities to multiple brain areas, such as the midbrain and hypothalamus, for immediate avoidance. Yet little is known about whether and how multi-sensory innate threat cues are integrated and conveyed from each sensory modality to the amygdala, a critical brain area for threat perception and learning. Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafascicular nucleus in the thalamus and external lateral parabrachial nucleus in the brainstem respond to multi-sensory threat cues from various sensory modalities and relay negative valence to the lateral and central amygdala, respectively. Both CGRP populations and their amygdala projections are required for multi-sensory threat perception and aversive memory formation. The identification of unified innate threat pathways may provide insights into developing therapeutic candidates for innate fear-related disorders." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "G-protein-coupled receptors (GPCR) are present at the cell surface in different conformational and oligomeric states. However, how these states impact GPCRs biological function and therapeutic targeting remains incompletely known. Here, we investigated this issue in living cells for the CC chemokine receptor 5 (CCR5), a major receptor in inflammation and the principal entry co-receptor for Human Immunodeficiency Viruses type 1 (HIV-1). We used TIRF microscopy and a statistical method to track and classify the motion of different receptor subpopulations. We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric states and exhibiting transient Brownian and restricted motions. These forms were stabilized differently by distinct ligands. In particular, agonist stimulation restricted the mobility of CCR5 and led to its clustering, a feature depending on β-arrestin, while inverse agonist stimulation exhibited the opposite effect. These results suggest a link between receptor activation and immobilization. Applied to HIV-1 envelope glycoproteins gp120, our quantitative analysis revealed agonist-like properties of gp120s. " Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects Ca 2+ Sensing but Not G Protein Interaction "The calcium-sensing receptor is a homodimeric class C G protein-coupled receptor (GPCR) that senses extracellular Ca2+ (Ca2+o ) via a dimeric extracellular Venus flytrap (VFT) unit that activates G protein-dependent signaling via twin Cysteine-rich domains linked to transmembrane heptahelical (HH) bundles. It plays a key role in the regulation of human calcium and thus mineral metabolism. However, the nature of interactions between VFT units and HH bundles, and the impacts of heterozygous or homozygous inactivating mutations, which have implications for disorders of calcium metabolism are not yet clearly defined. Herein we generated CaSR-GABAB1 and CaSR-GABAB2 chimeras subject to GABAB -dependent endoplasmic reticulum sorting to traffic mutant heterodimers to the cell surface. Transfected HEK-293 cells were assessed for Ca2+o -stimulated Ca2+i mobilization using mutations in either the VFT domains and/or HH bundle intraloop-2 or intraloop-3. When the same mutation was present in both VFT domains of receptor dimers, analogous to homozygous neonatal severe hyperparathyroidism (NSHPT), receptor function was markedly impaired. Mutant heterodimers containing one wild-type (WT) and one mutant VFT domain, however, corresponding to heterozygous familial hypocalciuric hypercalcemia type-1 (FHH-1), supported maximal signaling with reduced Ca2+o potency. Thus two WT VFT domains were required for normal Ca2+o potency and there was a pronounced gene-dosage effect. In contrast, a single WT HH bundle was insufficient for maximal signaling and there was no functional difference between heterodimers in which the mutation was present in one or both intraloops; ie, no gene-dosage effect. Finally, we observed that the Ca2+o -stimulated CaSR operated exclusively via signaling in-trans and not via combined in-trans and in-cis signaling. We consider how receptor asymmetry may support the underlying mechanisms. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)." Read more at the source #DrGPCR #GPCR #IndustryNews

Biased pharmacological modulators provide potential therapeutic benefits, including greater pharmacodynamic

TRPV4 to suppress astrocyte activation and to relieve neuropathic pain GPCRs in Oncology and Immunology Systems Pharmacodynamic Model of Combination Gemcitabine and Trabectedin in Pancreatic Cancer Cells.

The chemokine receptor system is implicated in a wide range of inflammatory, autoimmune and infectious and in recent years attention has increasingly focused on cancer, where tumors hijack the chemokine system lot of effort has been put forward to target CKRs especially in cancer, nevertheless, targeting this system agonists for CXCR3 further substantiated the notion that redundancy is not a feature of the chemokine system In the chemokine-receptor system, different chemokines are able to activate different pathways, which

In the cardiovascular system, ORs have the potential to operate as the main carriers of endogenously In the gastrointestinal system, ORs may significantly contribute to abnormal bowel functions. In the genito-urinary system, the activation of ORs was shown to influence the motility of spermatozoa In the nervous system, although there is limited data, it has been suggested that ORs adopt functions in the central nervous system.

October 2022 "The cAMP-dependent protein kinase (PKA) system represents a primary cell-signaling pathway throughout systems and across species. While limited, human studies infer differential regulation of the PKA system in obese compared to lean

The immune system depends on chemokines to direct cell migration during immune surveillance and inflammation However, an imbalance in the chemokine system can also contribute to various diseases, such as inflammatory glycosaminoglycans (GAGs) to regulate the movement of leukocytes throughout the body, ensuring a functional immune system

Affinity-Based Probe to Profile Endogenous Human Adenosine A3 Receptor Expression Pharmacokinetics and Pharmacodynamics

(IELs) are thought to calibrate glucagon-like peptide 1 (GLP-1) bioavailability, thereby regulating systemic anti-inflammatory actions of GLP-1RAs require the gut IEL GLP-1R to selectively restrain local and systemic GLP-1R activation in gut IELs to modulation of microbiota composition and control of intestinal and systemic

The opioid system is one of the most important in regulating the response to nociception, i.e. the response of the nervous system to painful stimuli; the 1970s marked the beginning of its study with the first discoveries which suggested that there were "binding sites" in the central nervous system that were The opioid system is composed of a set of major endogenous opioid peptides (EOPs): β-endorphin, enkephalins in driving intracellular signaling and reinforce the role of β-arrestins in the physiological opioid system

In particular, CBD is able to modulate different receptors in the endocannabinoid system, some of which Notably, while CBD is able to antagonize some GPCRs in the endocannabinoid system, it also seems to activate to characterize the GPR55 complexes correctly differentiate the agonist-bound and antagonist-bound systems utilized to characterize the CB1 complexes correctly differentiate the agonist-bound and antagonist-bound systems

leukocyte populations make it an ideal tissue to study interactions between the nervous and immune systems surface, alterations in disease settings, and the possible therapeutic potential of targeting these systems

GPCRs in various diseases, such as cardiovascular diseases, renal diseases, autoimmune diseases such as systemic sclerosis or systemic lupus erythematosus.