ArticleThe Journal of pharmacology and experimental therapeutics2009
Selectivity of agonists for the active state of M1 to M4 muscarinic receptor subtypes.
Article in The Journal of pharmacology and experimental therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
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- Insights into the mechanism by which atropine inhibits myopia: evidence against cholinergic hyperactivity and modulation of dopamine release.British journal of pharmacology · 2021Article
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- Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR.Science (New York, N.Y.) · 2020Article
- Fine Tuning Muscarinic Acetylcholine Receptor Signaling Through Allostery and Bias.Frontiers in pharmacology · 2020Review
- Cortical network dynamics are coupled with cognitive aging in rats.Hippocampus · 2019Article
- The muscarinic agonist pilocarpine modifies cocaine-reinforced and food-reinforced responding in rats: comparison with the cholinesterase inhibitor tacrine.Behavioural pharmacology · 2019Article
- Acetylcholine signaling system in progression of lung cancers.Pharmacology & therapeutics · 2019Review
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- Luciferase complementation based-detection of G-protein-coupled receptor activity.BioTechniques · 2018Article
- A method for the quantification of biased signalling at constitutively active receptors.British journal of pharmacology · 2018Article
- A Complementary Scale of Biased Agonism for Agonists with Differing Maximal Responses.Scientific reports · 2017Article
- Systematic errors in detecting biased agonism: Analysis of current methods and development of a new model-free approach.Scientific reports · 2017Article
- Receptor Activity-modifying Protein-directed G Protein Signaling Specificity for the Calcitonin Gene-related Peptide Family of Receptors.The Journal of biological chemistry · 2016Article
- Biased ligand quantification in drug discovery: from theory to high throughput screening to identify new biased μ opioid receptor agonists.British journal of pharmacology · 2016Article
- Human Neuropeptide S Receptor Is Activated via a Gαq Protein-biased Signaling Cascade by a Human Neuropeptide S Analog Lacking the C-terminal 10 Residues.The Journal of biological chemistry · 2016Article
- Gaddum Memorial Lecture 2014: receptors as an evolving concept: from switches to biased microprocessors.British journal of pharmacology · 2015Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We measured the intrinsic relative activity (RA(i)) of muscarinic agonists to detect possible selectivity for receptor subtypes and signaling pathways. RA(i) is a relative measure of the microscopic affinity constant of an agonist for the active state of a GPCR expressed relative to that of a standard agonist. First, we estimated RA(i) values for a panel of agonists acting at the M(4) muscarinic receptor coupled to three distinct G-protein pathways: G(i) inhibition of cAMP accumulation, G(s) stimulation of cAMP accumulation, and G alpha(15) stimulation of phosphoinositide hydrolysis. Our results show similar RA(i) values for each agonist, suggesting that the same active state of the M(4) receptor triggers the activation of the three G proteins. We also estimated RA(i) values for agonists across M(1) to M(4) muscarinic subtypes stably transfected in Chinese hamster ovary cells. Our results show selectivity of McN-A-343 [4-I-[3-chlorophenyl]carbamoyloxy)-2-butynyltrimethylammnonium chloride] for the M(1) and M(4) subtypes and selectivity of pilocarpine for the M(1) and M(3) subtypes. The other agonists tested lacked marked selectivity among M(1) to M(4) receptors. Finally, we estimated RA(i) values from published literature on M(1), M(2), and M(3) muscarinic responses and obtained results consistent with our own studies. Our results show that the RA(i) estimate is a useful receptor-dependent measure of agonist activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.