ArticleBritish journal of pharmacology2003
Evidence for cross-talk between M2 and M3 muscarinic acetylcholine receptors in the regulation of second messenger and extracellular signal-regulated kinase signalling pathways in Chinese hamster ovary cells.
Article in British journal of pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 35 citations in OpenAlex.
- Neurokinin-2 receptor negatively modulates substance P responses by forming complex with Neurokinin-1 receptor.Cell & bioscience · 2023Article
- Balanced modulation of neuromuscular synaptic transmission via M1 and M2 muscarinic receptors during inhibition of cholinesterases.Scientific reports · 2022Article
- Integration and Spatial Organization of Signaling by G Protein-Coupled Receptor Homo- and Heterodimers.Biomolecules · 2021Review
- Acetylcholine-dependent upregulation of TASK-1 channels in thalamic interneurons by a smooth muscle-like signalling pathway.The Journal of physiology · 2017Article
- A New Generation of FRET Sensors for Robust Measurement of Gαi1, Gαi2 and Gαi3 Activation Kinetics in Single Cells.PloS one · 2016Article
- Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders.CNS neuroscience & therapeutics · 2014Review
- Article
- The cellular building blocks of breathing.Comprehensive Physiology · 2012Review
- Membrane cholesterol content influences binding properties of muscarinic M2 receptors and differentially impacts activation of second messenger pathways.European journal of pharmacology · 2009Article
- Interaction of P2 purinergic receptors with cellular macromolecules.Naunyn-Schmiedeberg's archives of pharmacology · 2008Review
- An investigation of whether agonist-selective receptor conformations occur with respect to M2 and M4 muscarinic acetylcholine receptor signalling via Gi/o and Gs proteins.British journal of pharmacology · 2005Article
- A homotropic two-state model and auto-antagonism.BMC pharmacology · 2004Article
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5 authors at 1 institution in 1 country.
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Abstract
1. We have examined possible mechanisms of cross-talk between the G(q/11)-linked M(3) muscarinic acetylcholine (mACh) receptor and the G(i/o)-linked M(2) mACh receptor by stable receptor coexpression in Chinese hamster ovary (CHO) cells. A number of second messenger (cyclic AMP, Ins(1,4,5)P(3)) and mitogen-activated protein kinase (ERK and JNK) responses stimulated by the mACh receptor agonist methacholine were examined in CHO-m2m3 cells and compared to those stimulated in CHO-m2 and CHO-m3 cell-lines, expressing comparable levels of M(2) or M(3) mACh receptors. 2. Based on comparisons between cell-lines and pertussis toxin (PTx) pretreatment to eliminate receptor-G(i/o) coupling, evidence was obtained for (i) an M(2) mACh receptor-mediated contribution to the predominantly M(3) mACh receptor-mediated Ins(1,4,5)P(3) response and (ii) a facilitation of the inhibitory effect of M(2) mACh receptor on forskolin-stimulated cyclic AMP accumulation by M(3) mACh receptor coactivation at low agonist concentrations (MCh 10(-9)-10(-6) M). 3. The most profound cross-talk effects were observed with respect to ERK activation. Thus, while MCh stimulated ERK activation in both CHO-m2 and CHO-m3 cells (pEC(50) values: 5.64+/-0.09 and 5.57+/-0.16, respectively), the concentration-effect relation was approx 50-fold left-shifted in CHO-m2m3 cells (pEC(50): 7.17+/-0.07). In addition, the ERK response was greater and more sustained in CHO-m2m3 cells. In contrast, only minor differences were seen in the time-courses and concentration-dependencies of JNK activation in CHO-m3 and CHO-m2m3 cells. 4. Costimulation of endogenous P2Y(2) purinoceptors also caused an approx 10-fold left-shift in the MCh-stimulated ERK response in CHO-m2 cells, suggesting that the G(q/11)/G(i/o) interaction to affect ERK activation is not specific to muscarinic receptors. 5. PTx pretreatment of cells had unexpected effects on ERK activation by MCh in both CHO-m2m3 and CHO-m3 cells. Thus, in CHO-m3 cells PTx pretreatment caused a marked left-shift in the MCh concentration-effect curve, while in PTx-treated CHO-m2m3 cells the maximal responsiveness was decreased, but the potency of MCh was only slightly affected. 6. The data presented here strongly suggest that cross-talk between M(2) and M(3) mACh receptors occurs at the level of both second messenger and ERK regulation. Further, these data provide novel insights into the involvement of G(i/o) proteins in both positive and negative modulation of ERK responses evoked by G protein-coupled receptors.
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