ArticleMolecular pharmacology2008
M3 muscarinic acetylcholine receptor-mediated signaling is regulated by distinct mechanisms.
Article in Molecular pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
90 citing papers in PubMed, 143 citations in OpenAlex.
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- Location bias: A "Hidden Variable" in GPCR pharmacology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Exploring neurotransmitters and their receptors for breast cancer prevention and treatment.Theranostics · 2023Review
- Control of GαScience advances · 2022Article
- Histamine via histamine H1 receptor enhances the muscarinic receptor-induced calcium response to acetylcholine in an enterochromaffin cell model.Clinical and experimental pharmacology & physiology · 2022Article
- Salivary gland function, development, and regeneration.Physiological reviews · 2022Review
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- Biased GPCR signaling: Possible mechanisms and inherent limitations.Pharmacology & therapeutics · 2020Review
- Characterization of an A-Type Muscarinic Acetylcholine Receptor and Its Possible Non-neuronal Role in the Oriental Armyworm,Frontiers in physiology · 2020Article
- Protein Kinase CK2-A Putative Target for the Therapy of Diabetes Mellitus?International journal of molecular sciences · 2019Review
- Chemerin-activated functions of CMKLR1 are regulated by G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 in inflammatory macrophages.Molecular immunology · 2019Article
- Role of Muscarinic Acetylcholine Receptors in Breast Cancer: Design of Metronomic Chemotherapy.Current clinical pharmacology · 2019Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We have used RNA interference previously to demonstrate that G protein-coupled receptor kinase 2 (GRK2) regulates endogenously expressed H1 histamine receptor in human embryonic kidney 293 cells. In this report, we investigate the regulation of endogenously expressed M(3) muscarinic acetylcholine receptor (M(3) mAChR). We show that knockdown of GRK2, GRK3, or GRK6, but not GRK5, significantly increased carbachol-mediated calcium mobilization. Stable expression of wild-type GRK2 or a kinase-dead mutant (GRK2-K220R) reduced calcium mobilization after receptor activation, whereas GRK2 mutants defective in Galpha(q) binding (GRK2-D110A, GRK2-R106A, and GRK2-R106A/K220R) had no effect on calcium signaling, suggesting that GRK2 primarily regulates G(q) after M(3) mAChR activation. The knockdown of arrestin-2 or arrestin-3 also significantly increased carbachol-mediated calcium mobilization. Knockdown of GRK2 and the arrestins also significantly enhanced carbachol-mediated activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), whereas prolonged ERK1/2 activation was only observed with GRK2 or arrestin-3 knockdown. We also investigated the role of casein kinase-1alpha (CK1alpha) and found that knockdown of CK1alpha increased calcium mobilization but not ERK activation. In summary, our data suggest that multiple proteins dynamically regulate M(3) mAChR-mediated calcium signaling, whereas GRK2 and arrestin-3 play the primary role in regulating ERK activation.
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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.