Journal ArticleDOI
Constitutive activity of muscarinic acetylcholine receptors
TLDR
The literature describing constitutive activity of the five muscarinic acetylcholine receptors in native and recombinant systems is reviewed and the possible physiological significance is discussed, incorporating information provided by targeted deletion of each of the Muscarinic subtypes.Abstract:
We review the literature describing constitutive activity of the five muscarinic acetylcholine receptors in native and recombinant systems and discuss the effect of constitutive activity on muscarinic pharmacology in the context of modern models of receptor activation. We include a summary of mutations found to cause constitutive activity and discuss the implications of these data for the structure, function, and activation mechanism of muscarinic receptors. Finally, we discuss the possible physiological significance of constitutive activity of muscarinic receptors, incorporating information provided by targeted deletion of each of the muscarinic subtypes.read more
Citations
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Journal ArticleDOI
Activation and dynamic network of the M2 muscarinic receptor.
Yinglong Miao,Sara E. Nichols,Paul M. Gasper,Vincent T. Metzger,J. Andrew McCammon,J. Andrew McCammon +5 more
TL;DR: Network analysis reveals that communication in the intracellular domains is greatly weakened during activation of the receptor, and highlights a dynamic network for allosteric regulation of the M2 receptor activation.
Journal ArticleDOI
Two distinct conformations of helix 6 observed in antagonist-bound structures of a β1-adrenergic receptor
Rouslan Moukhametzianov,Tony Warne,Patricia C. Edwards,Maria Josefa Serrano-Vega,Andrew G. W. Leslie,Christopher G. Tate,Gebhard F. X. Schertler +6 more
TL;DR: Eight new structures of β1AR–M23 are compared, determined from crystallographically independent molecules in four different crystals with three different antagonists bound in the inactive R state and show clear electron density for cytoplasmic loop 3 linking transmembrane helices 5 and 6 that had not been seen previously.
Journal ArticleDOI
Accelerated molecular dynamics simulations of ligand binding to a muscarinic G-protein-coupled receptor
TL;DR: In this paper, an accelerated molecular dynamics (aMD) is proposed to simulate processes of ligand binding to a G-protein-coupled receptor (GPCR), in this case the M3 muscarinic receptor, which is a target for treating many human diseases, including cancer, diabetes and obesity.
Journal ArticleDOI
On the discovery and development of pimavanserin: a novel drug candidate for Parkinson's psychosis
TL;DR: Pimavanserin demonstrated good safety and tolerability and did not worsen motoric symptoms as assessed by the unified Parkinson’s disease rating scale parts II and III, and may offer a viable treatment option for patients suffering from PDP.
Journal ArticleDOI
Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.
Monica S. Guzman,Xavier De Jaeger,Xavier De Jaeger,Sanda Raulic,Ivana A. Souza,Ivana A. Souza,Alex X. Li,Susanne Schmid,Ravi S. Menon,Raul R. Gainetdinov,Raul R. Gainetdinov,Marc G. Caron,Robert Bartha,Vania F. Prado,Marco A. M. Prado +14 more
TL;DR: A novel mouse model that eliminates cholinergic neurotransmission in the striatum while leaving glutamate release intact reveals differential effects on cocaine-induced behavior and dopaminergic responses.
References
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Journal ArticleDOI
Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.
TL;DR: The analysis described shows K I does not equal I 50 when competitive inhibition kinetics apply; however, K I is equal to I 50 under conditions of either noncompetitive or uncompetitive kinetics.
Journal ArticleDOI
Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor
Krzysztof Palczewski,Takashi Kumasaka,Tetsuya Hori,Craig A. Behnke,H. Motoshima,Brian A. Fox,I. Le Trong,David C. Teller,Tetsuji Okada,Ronald E. Stenkamp,Masaki Yamamoto,Masashi Miyano +11 more
TL;DR: This article determined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution and found that the highly organized structure in the extracellular region, including a conserved disulfide bridge, forms a basis for the arrangement of the sevenhelix transmembrane motif.
Book ChapterDOI
[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors
TL;DR: This chapter discusses the integrated methods for the construction of three-dimensional models and computational probing of structure–function relations in G protein-coupled receptors (GPCR) and expects increased rate of success achieved by molecular modeling and computational simulation methods in providing structural insights relevant to the functions of biological molecules.
Journal ArticleDOI
A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor.
TL;DR: In this paper, a ternary complex model was used to fit the data with high accuracy under conditions where the ligand used is either a full or a partial agonist and where the system is altered by the addition of guanine nucleotide or after treatment with group-specific reagents.
Journal ArticleDOI
Muscarinic Receptor Subtypes
TL;DR: The aim of this review is to discuss the structure, function, and binding properties of the different muscarinic receptor species, attempting where possible to coordinate the diverse experimental data into a uniform picture.