Development of a Radioligand, [3H]LY2119620, to Probe the Human M2 and M4 Muscarinic Receptor Allosteric Binding Sites

2014 ◽  
Vol 86 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Douglas A. Schober ◽  
Carrie H. Croy ◽  
Hongling Xiao ◽  
Arthur Christopoulos ◽  
Christian C. Felder
Keyword(s):  
Muscarinic Receptor ◽  
Binding Sites ◽  
Allosteric Binding Sites ◽  
M4 Muscarinic Receptor

Therapeutic Opportunities of Targeting Allosteric Binding Sites on the Calcium-Sensing Receptor

2021 ◽  
Vol 4 (2) ◽  
pp. 666-679
Author(s):  
Jiayin Diao ◽  
Aaron DeBono ◽  
Tracy M. Josephs ◽  
Jane E. Bourke ◽  
Ben Capuano ◽  
...  
Keyword(s):  
Binding Sites ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Allosteric Binding Sites

Location and quantification of muscarinic receptor subtypes in rat pons: implications for REM sleep generation

1997 ◽  
Vol 273 (3) ◽  
pp. R896-R904 ◽  
Author(s):  
H. A. Baghdoyan
Keyword(s):  
Muscarinic Receptor ◽  
Reticular Formation ◽  
Muscarinic Receptors ◽  
Rem Sleep ◽  
Binding Sites ◽  
Reticular Nucleus ◽  
Homogeneous Distribution ◽  
Receptor Subtypes ◽  
Pontine Reticular Formation ◽  
Muscarinic Receptor Subtypes

Microinjecting cholinomimetics into the pontine reticular formation produces a state that resembles natural rapid eye movement (REM) sleep. Evocation of this REM sleeplike states is anatomically site dependent within the pons and is mediated by muscarinic receptors. The cellular and molecular mechanisms underlying cholinergic REM sleep generation and muscarinic receptor subtype involvement remain to be specified. This study tested the hypothesis that muscarinic receptor subtypes are differentially distributed within the oral and caudal divisions of rat pontine reticular nucleus. In vitro receptor autoradiography was used to localize and quantify M1, M2, and M3 binding sites in the pontine reticular formation and in pontine brain stem regions known to regulate REM sleep. M1-M3 binding sites were present in some REM sleep-related nuclei, such as dorsal raphe and locus ceruleus. The pontine reticular formation was found to have a homogeneous distribution of M2 binding sites across its rostral to caudal extent, indicating that anatomic specificity of cholinergic REM sleep induction cannot be accounted for by a differential density of muscarinic receptors.

Altered distribution of M2 and M4 muscarinic receptor expression in vitiligo

2010 ◽  
Vol 38 (5) ◽  
pp. 493-497
Author(s):  
Sirintip CHAICHALOTORNKUL ◽  
Montree UDOMPATAIKUL ◽  
Udomsri SHOWPITTAPORNCHAI ◽  
Piti PALUNGWACHIRA ◽  
Wisuit PRADIDARCHEEP
Keyword(s):  
Muscarinic Receptor ◽  
Receptor Expression ◽  
M4 Muscarinic Receptor

scholarly journals Identification and Pharmacological Characterization of Multiple Allosteric Binding Sites on the Free Fatty Acid 1 Receptor

2012 ◽  
Vol 82 (5) ◽  
pp. 843-859 ◽  
Author(s):  
Daniel C.-H. Lin ◽  
Qi Guo ◽  
Jian Luo ◽  
Jane Zhang ◽  
Kathy Nguyen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Binding Sites ◽  
Pharmacological Characterization ◽  
Allosteric Binding Sites

The quest for allosteric binding sites in mGluRs group III

2012 ◽  
Vol 64 (2) ◽  
pp. 471-472
Author(s):  
Paulina Chorobik ◽  
Piotr Brański ◽  
Grzegorz Burnat ◽  
Barbara Chruścicka ◽  
Tomasz Lenda ◽  
...  
Keyword(s):  
Binding Sites ◽  
Group Iii ◽  
Allosteric Binding Sites

scholarly journals Functional tunability from a distance: Rheostat positions influence allosteric coupling between two distant binding sites

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tiffany Wu ◽  
Liskin Swint-Kruse ◽  
Aron W. Fenton
Keyword(s):  
Binding Sites ◽  
Functional Outcomes ◽  
Human Liver ◽  
Full Range ◽  
Allosteric Coupling ◽  
Multiple Parameters ◽  
Wide Range ◽  
Allosteric Binding Sites ◽  
Fructose 1,6 Bisphosphate ◽  
Effector Binding

AbstractFor protein mutagenesis, a common expectation is that important positions will behave like on/off “toggle” switches (i.e., a few substitutions act like wildtype, most abolish function). However, there exists another class of important positions that manifests a wide range of functional outcomes upon substitution: “rheostat” positions. Previously, we evaluated rheostat positions located near the allosteric binding sites for inhibitor alanine (Ala) and activator fructose-1,6-bisphosphate (Fru-1,6-BP) in human liver pyruvate kinase. When substituted with multiple amino acids, many positions demonstrated moderate rheostatic effects on allosteric coupling between effector binding and phosphoenolpyruvate (PEP) binding in the active site. Nonetheless, the combined outcomes of all positions sampled the full range of possible allosteric coupling (full tunability). However, that study only evaluated allosteric tunability of “local” positions, i.e., positions were located near the binding sites of the allosteric ligand being assessed. Here, we evaluated tunability of allosteric coupling when mutated sites were distant from the allosterically-coupled binding sites. Positions near the Ala binding site had rheostatic outcomes on allosteric coupling between Fru-1,6-BP and PEP binding. In contrast, positions in the Fru-1,6-BP site exhibited modest effects on coupling between Ala and PEP binding. Analyzed in aggregate, both PEP/Ala and PEP/Fru-1,6-BP coupling were again fully tunable by amino acid substitutions at this limited set of distant positions. Furthermore, some positions exhibited rheostatic control over multiple parameters and others exhibited rheostatic effects on one parameter and toggle control over a second. These findings highlight challenges in efforts to both predict/interpret mutational outcomes and engineer functions into proteins.

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