Chapter 12 Allosteric regulation of muscarinic receptors
References (17)
- et al.
Allosteric regulation of cloned m1--m5 muscarinic receptor subtypes.
Biochem. Pharmacol.
(1991) - et al.
Allosteric antagonists of the muscarinic acetylcholine receptor.
Biochem. Pharmacol.
(1991) Molecular basis of muscarinic acetylcholine receptor function.
Trends Pharmacol. Sci.
(1993)- et al.
Allosteric regulation of G-protein linked receptors.
Biochem. Soc. Trans.
(1995) - et al.
The inhibitory effect of gallamine on muscarinic receptors.
Br. J. Pharmacol.
(1976) - et al.
Heterogeneity of binding sites on cardiac muscarinic receptors induced by the neuromuscular blocking agents gallamine and pancuronium.
Mol. Pharmacol.
(1983) - et al.
Use of chimeric muscarinic receptors to investigate epitopes involved in allosteric interactions.
Mol. Pharmacol.
(1993) - et al.
Muscarinic receptor subtypes.
Annu. Rev. Pharmacol.
(1990)
Cited by (31)
CB<inf>1</inf> allosteric modulators and their therapeutic potential in CNS disorders
2021, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :For example, subtype selectivity for muscarinic receptors was obtained via the development of an muscarinic M1 receptor PAM (Jones et al., 2008). Second, many allosteric ligands have the potential to act exclusively in the presence of receptor agonists, which therefore, allows allosteric modulators to maintain the spatial and temporal signaling of the native receptor (Birdsall et al., 1996; Conn et al., 2009). Lastly, orthosteric ligands can have challenging physiochemical and pharmacokinetic properties that make drug discovery difficult (i.e. peptide receptors).
Allosteric modulation of a cannabinoid G protein-coupled receptor: Binding site elucidation and relationship to G protein signaling
2014, Journal of Biological ChemistryCitation Excerpt :This is perhaps best exemplified by the muscarinic family of receptors, in which a common allosteric binding site has been reported in all five muscarinic receptor subtypes; this site is located in an EC region (38). It has been hypothesized that by binding more extracellularly than orthosteric agonists, allosteric modulators may sterically hinder an orthosteric agonist from exiting the receptor (39–41). However, unlike many GPCRs that bind hydrophilic ligands that enter the receptor via the receptor's extracellular surface, the cannabinoid receptors bind hydrophobic lipid-derived ligands; this fundamental difference in hydrophobicity may suggest that these hydrophobic ligands enter by an alternative route.
A novel biased allosteric compound inhibitor of parturition selectively impedes the prostaglandin F2α-mediated Rho/ROCK Signaling Pathway
2010, Journal of Biological ChemistryCitation Excerpt :The clinical use of allosteric compounds has recently attracted more attention (57–59). These modulators can be used at saturating concentrations, because their effects are only revealed in the presence of endogenous ligands (e.g. neutral allosteric ligands), potentially reducing adverse effects (60–62). The design of allosteric ligands with biased signaling properties, as in the case of PDC113.824, offers not only the advantage of specificity for a single GPCR, but also selectivity for a specific subset of signaling pathways, further reducing unwanted side effects.
Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?
2007, Trends in Pharmacological SciencesDesigning Human m<inf>1</inf> Muscarinic Receptor-Targeted Hydrophobic Eigenmode Matched Peptides As Functional Modulators
2004, Biophysical JournalCitation Excerpt :Christopoulos and Kenakin (2002) have reviewed allosteric mechanisms using point mutagenic and chimeric exchange studies in muscarinic receptors assessed by isotopic ligand binding and cellular function. They suggest that mi allosteric modulators such as gallamine, alcuronium, and the bis-ammonium compounds have multiple extracellular sites of action, particularly in the sequence neighborhoods of the extracellular loops, e2 and e3 (Birdsall et al., 1996; Christopoulos and Kenakin, 2002; Christopoulos et al., 1998; Lee and el-Fakahany, 1991; Matsui et al., 1995). Relevant to our program designing receptor-targeted, hydrophobic mode-matched peptides, it is interesting that antibodies raised to these extracellular loop polypeptide sequences have been shown to allosterically modulate and/or activate GPCRs (abu Alla et al., 1996; Mijares et al., 1996, 2000).
Allosteric modulators of G-protein-coupled receptors
2003, Current Opinion in Pharmacology