PRKC Apoptosis WT1 Regulator Protein

2020 ◽  
Author(s):  
Keyword(s):  
Regulator Protein

Diversified Synthetic Pathway of 1, 4-Dihydropyridines: A Class of Pharmacologically Important Molecules

2020 ◽  
Vol 20 ◽  
Author(s):  
Shubham Khot ◽  
Pratibha B. Auti ◽  
Samrat A. Khedkar
Keyword(s):  
Pharmacological Action ◽  
Heterocyclic Ring ◽  
Channel Blockers ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Current Review ◽  
Regulator Protein ◽  
Cystic Fibrosis Transmembrane ◽  
Hiv 1 ◽  
Dihydropyridine Derivatives

: The current review discusses the different synthetic pathways for one of the most important and interesting heterocyclic ring systems 1,4-dihydropyridine. This cyclic system depicts diverse pharmacological action at several receptors, channels, and enzymes. Dihydropyridine moiety plays an important role in several calcium-channel blockers. Moreover, it has been exploited for the treatment of a variety of cardiovascular diseases due to its potential antihypertensive, anti-angina, vasodilator, and cardiac depressant activities. Furthermore, it also shows antibacterial, anticancer, antileishmanial, anticoagulant, anticonvulsant, anti-tubercular, antioxidant, antiulcer, and neuroprotective properties. Several reports have demonstrated dihydropyridine derivatives as a potentiator of cystic fibrosis transmembrane conductance regulator protein, potent antimalarial agent and HIV-1 protease inhibitor. Herein, we have briefly reviewed different novel chemistry and synthesis of 1,4-dihydropyridine.

scholarly journals Biosensors Monitor Ligand-Selective Effects at Kappa Opioid Receptors

2021 ◽  
Author(s):  
Lucie Oberhauser ◽  
Miriam Stoeber
Keyword(s):  
Subcellular Location ◽  
Receptor Activation ◽  
Cellular Level ◽  
Two Dimensions ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Downstream Signaling ◽  
Regulator Protein ◽  
Cellular Context ◽  
Selective Effects

AbstractThe kappa opioid receptor (KOR) has emerged as a promising therapeutic target for pain and itch treatment. There is growing interest in biased agonists that preferentially activate select signaling pathways downstream of KOR activation on the cellular level due to their therapeutic promise in retaining the analgesic and antipruritic effects and eliminating the sedative and dysphoric effects of KOR signaling on the physiological level. The concept of ligand-selective signaling includes that biased ligands promote KOR to selectively recruit one transducer or regulator protein over another, introducing bias into the signaling cascade at the very receptor-proximal level. Measuring agonist effects directly at the receptor has remained challenging and previous studies have focused on inferring agonist-selective KOR engagement with G protein relative to β-arrestin based on downstream signaling readouts. Here we discuss novel strategies to directly assess ligand-selective effects on receptor activation using KOR-interacting biosensors. The conformation-specific cytoplasmic biosensors are disconnected from the endogenous signaling machinery and provide a direct receptor-proxy readout of ligand effects in living cells. Receptor–biosensor interaction is ligand concentration dependent and can be used to determine relative ligand potency and efficacy. In addition, the biosensors reveal the existence of two dimensions of agonist bias in the cellular context: Firstly, agonists can selectively produce discrete protein-engaged KOR states and secondly, agonists can differ in the precise subcellular location at which they activate KOR. We discuss the value and the limitations of using orthogonal receptor-interacting biosensors in the quest to understand functional selectivity amongst KOR agonists in the cellular context.

Liquid secretion inhibitors reduce mucociliary transport in glandular airways

2002 ◽  
Vol 283 (2) ◽  
pp. L329-L335 ◽  
Author(s):  
Stephen T. Ballard ◽  
Laura Trout ◽  
Anil Mehta ◽  
Sarah K. Inglis
Keyword(s):  
Beat Frequency ◽  
Anion Channel ◽  
Ciliary Beat Frequency ◽  
Mucociliary Transport ◽  
Transmembrane Conductance Regulator ◽  
Inhibitory Effects ◽  
Transmembrane Conductance ◽  
Regulator Protein ◽  
Liquid Absorption ◽  
Cf Transmembrane Conductance Regulator

Because of its possible importance in cystic fibrosis (CF) pulmonary pathogenesis, the effect of anion and liquid secretion inhibitors on airway mucociliary transport was examined. When excised porcine tracheas were treated with ACh to induce gland liquid secretion, the rate of mucociliary transport was increased nearly threefold from 2.5 ± 0.5 to 6.8 ± 0.8 mm/min. Pretreatment with both bumetanide and dimethylamiloride (DMA), to respectively inhibit Cl− and HCO[Formula: see text]secretion, significantly reduced mucociliary transport in the presence of ACh by 92%. Pretreatment with the anion channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid similarly reduced mucociliary transport in ACh-treated airways by 97%. These agents did not, however, reduce ciliary beat frequency. Luminal application of benzamil to block liquid absorption significantly attenuated the inhibitory effects of bumetanide and DMA on mucociliary transport. We conclude that anion and liquid secretion is essential for normal mucociliary transport in glandular airways. Because the CF transmembrane conductance regulator protein likely mediates Cl−, HCO[Formula: see text], and liquid secretion in normal glands, we speculate that impairment of gland liquid secretion significantly contributes to defective mucociliary transport in CF.

Crystal structure of the T4 regA translational regulator protein at 1.9 A resolution

Science ◽  
1995 ◽  
Vol 268 (5214) ◽  
pp. 1170-1173 ◽  
Author(s):  
C Kang ◽  
R Chan ◽  
I Berger ◽  
C Lockshin ◽  
L Green ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Regulator Protein

scholarly journals Genetic Analysis of Colistin Resistance in Salmonella enterica Serovar Typhimurium

2009 ◽  
Vol 53 (6) ◽  
pp. 2298-2305 ◽  
Author(s):  
Song Sun ◽  
Aurel Negrea ◽  
Mikael Rhen ◽  
Dan I. Andersson
Keyword(s):  
Mutation Rate ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Regulatory System ◽  
Clinical Settings ◽  
Missense Mutations ◽  
Regulator Protein ◽  
Serovar Typhimurium ◽  
Sensor Kinases ◽  
Genes Encoding

ABSTRACT Colistin is a cyclic cationic peptide that kills gram-negative bacteria by interacting with and disrupting the outer membrane. We isolated 44 independent mutants in Salmonella enterica serovar Typhimurium with reduced susceptibility to colistin and identified 27 different missense mutations located in the pmrA and pmrB genes (encoding the regulator and sensor of a two-component regulatory system) that conferred increased resistance. By comparison of the two homologous sensor kinases, PmrB and EnvZ, the 22 missense mutations identified in pmrB were shown to be located in four different structural domains of the protein. All five pmrA mutations were located in the phosphate receiver domain of the regulator protein. The mutants appeared at a mutation rate of 0.6 × 10−6 per cell per generation. The MICs of colistin for the mutants increased 2- to 35-fold, and the extent of killing was reduced several orders of magnitude compared to the susceptible strain. The growth rates of the mutants were slightly reduced in both rich medium and M9-glycerol minimal medium, whereas growth in mice appeared unaffected by the pmrA and pmrB mutations. The low fitness costs and the high mutation rate suggest that mutants with reduced susceptibility to colistin could emerge in clinical settings.

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