A5055902763- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Chemical Synthesis and Analysis
- Respiratory viral infections research
- Immune Response and Inflammation
- Neuroscience and Neuropharmacology Research
- Computational Drug Discovery Methods
- Fatty Acid Research and Health
- Nicotinic Acetylcholine Receptors Study
- Respiratory and Cough-Related Research
- Monoclonal and Polyclonal Antibodies Research
- Asthma and respiratory diseases
McGill University
2023
J. Craig Venter Institute
1998
University of Maryland, Baltimore
1988-1990
University of Baltimore
1990
G protein–coupled receptors engage both proteins and β-arrestins, their coupling can be biased by ligands mutations. Here, to resolve structural elements mechanisms underlying effector the angiotensin II (AngII) type 1 receptor (AT1R), we combined alanine scanning mutagenesis of entire sequence with pharmacological profiling Gα q β-arrestin engagement mutant molecular dynamics simulations. We showed that AT1R involved a large number residues spread across receptor, whereas fewer regions...
Viral infections increase vagally mediated reflex bronchoconstriction. Decreased function of inhibitory M2 muscarinic receptors on the parasympathetic nerve endings is likely to contribute increased acetylcholine release. In this study, we used cultured airway neurons determine effects parainfluenza virus and interferon (IFN)-gamma release, receptor function, gene expression. control cultures, electrically stimulated release when were blocked using atropine (10(-)5 M) decreased these...
The purpose of our study was to investigate the interactions allosteric antagonists at individual m1, m2 and m3 muscarinic receptor subtypes. This achieved through use transformed Chinese hamster ovary cells stably expressing rat m1 or genes. A homogeneous population subtype obtained from heart tissue. Our data indicate that cardioselective (gallamine, methoctramine, AF-DX 116 himbacine) display following rank order potency for both displacing ligand binding primary site on allosterically...
The binding profile of the positively charged muscarinic antagonist, gallamine, was studied in rat heart homogenates. A proportion sites labeled by tertiary ligands [( 3H]quinuclidinyl benzilate (QNB) and [3H]atropine) were inaccessible to their quaternary analogs 3H]N-methyl-QNB (NMeQNB) [3H]-N-methylscopolamine (NMS)] or gallamine. Whereas gallamine displaced [3H]NMeQNB with high affinity, biphasic competition curves observed using [3H]NMS only at higher ligand concentrations. rank order...
The allosteric effects and subtype selectivity of methoctramine on neuronal muscarinic receptors in N1E-115 cells two different rat brain regions (cerebral cortex striatum) were assessed. Saturation isotherms [3H]N-methylscopolamine binding, performed dissociated cerebral cortex, showed that reduced the Bmax a concentration-dependent manner. Furthermore, this compound slowed rate dissociation bound same tissue preparations. Low concentrations (less than or equal to 1 microM) antagonized...