Search results for " agonism"
showing 6 items of 6 documents
Biased Agonism in Drug Discovery—Is It Too Soon to Choose a Path?
2018
A single receptor can activate multiple signaling pathways that have distinct or even opposite effects on cell function. Biased agonists stabilize receptor conformations preferentially stimulating one of these pathways, and therefore allow a more targeted modulation of cell function and treatment of disease. Dedicated development of biased agonists has led to promising drug candidates in clinical development, such as the G protein-biased µ opioid receptor agonist oliceridine. However, leveraging the theoretical potential of biased agonism for drug discovery faces several challenges. Some of these challenges are technical, such as techniques for quantitative analysis of bias and development …
Desensitization of cAMP Accumulation via Human β3-Adrenoceptors Expressed in Human Embryonic Kidney Cells by Full, Partial, and Biased Agonists
2019
β3-Adrenoceptors couple not only to cAMP formation but, at least in some cell types, also to alternative signaling pathways such as phosphorylation of extracellular signal-regulated kinase (ERK). β3-Adrenoceptor agonists are used in long-term symptomatic treatment of the overactive bladder syndrome; it is only poorly understood which signaling pathway mediates the clinical response and whether it undergoes agonist-induced desensitization. Therefore, we used human embryonic kidney cells stably transfected with human β3-adrenoceptors to compare coupling of ligands with various degrees of efficacy, including biased agonists, to cAMP formation and ERK phosphorylation, particularly regarding des…
A systematic review of inverse agonism at adrenoceptor subtypes
2020
As many, if not most, ligands at G protein-coupled receptor antagonists are inverse agonists, we systematically reviewed inverse agonism at the nine adrenoceptor subtypes. Except for β3-adrenoceptors, inverse agonism has been reported for each of the adrenoceptor subtypes, most often for β2-adrenoceptors, including endogenously expressed receptors in human tissues. As with other receptors, the detection and degree of inverse agonism depend on the cells and tissues under investigation, i.e., they are greatest when the model has a high intrinsic tone/constitutive activity for the response being studied. Accordingly, they may differ between parts of a tissue, for instance, atria vs. ventricles…
PUÒ IL POTERE ESSERE NEUTRALE? AGONISMO, RESISTENZA E SOGGETTIVITÀ NOTE SUL FOUCAULT DI BRIGAGLIA
2020
In questo articolo sottopongo ad alcune considerazioni critiche la tesi di Brigaglia secondo la quale il Foucault degli anni ’80 avrebbe maturato ed esplicitato una concezione del potere, neutrale e pragmatica, qualitativamente molto diversa da quella, conflittualista e ultra-radicale, che attraverserebbe invece i suoi lavori degli anni ’70. In contrario, sosterrò che, pur con diverse accentazioni, il pensiero di Foucault è costantemente informato all’idea secondo cui ogni relazione di potere comporta sempre un agonismo, attuale o anche solo potenziale, che ha come contraltare una resistenza, anche questa attuale o potenziale, del bersaglio; sosterrò, altresì, che questa dinamica potere-res…
Effects of the benzodiazepine inverse agonist FG7142 on the structure of anxiety-related behavior of male Wistar rats tested in hole board
2016
Little is known about the structural characteristics of the behavior of rats with enhanced anxiety level. To fill this gap, a study was undertaken where effects of an anxiogenic drug were examined on behavioral structure of rats tested in hole board.This study investigates effects of increased anxiety level on the structure of the behavior of rats tested in hole board METHODS: Different doses of FG7142 (1, 4, 8 mg/kg IP), a potent anxiety-inducing drug, were administered to three groups of male Wistar rats. A further group was administered saline. Experiments were recorded through a digital camera. Quantitative and multivariate approaches were applied.Percent distributions and durations sho…
Sport and Quality of Life
2022
Negli ultimi trent’anni lo sport ha assunto un significato molto rilevante nella vita delle persone e, seppure con notevoli differenze, sia nei paesi a sviluppo economico avanzato, sia in quelli in via di sviluppo. A livello individuale, esso ha costituito un’area di investimento identitario quando ha assunto la forma di sport spettacolo del quale fruire, alimentando la pratica del tifo e il fandom o costituendo il modello di uno stile di vita vincente; ma anche quando ha assunto la forma di pratica del tempo libero attraverso la quale tenersi in forma, facendo crescere, in questo caso, la diffusione di una cultura della salute e del benessere. Si tratta di due modalità di approcciare al co…