Dual effects of muscarinic M2 acetylcholine receptors on the synthesis of cyclic AMP in CHO cells: dependence on time, receptor density and receptor agonists

@article{Michal2001DualEO,
  title={Dual effects of muscarinic M2 acetylcholine receptors on the synthesis of cyclic AMP in CHO cells: dependence on time, receptor density and receptor agonists},
  author={Pavel Michal and Michaela Lys{\'i}kov{\'a} and Stanislav Tuc̆ek},
  journal={British Journal of Pharmacology},
  year={2001},
  volume={132}
}
Muscarinic M2 receptors normally inhibit the production of cyclic AMP via Gi proteins, but a stimulatory component occurs in their effect at high agonist concentrations, believed to be based on the activation of Gs proteins. We investigated the conditions which determine the occurrence and extent of the stimulatory component in CHO cells stably expressing muscarinic M2 receptors. Biphasic concentration‐response curves (decline followed by return towards control values) were obtained after 10… Expand
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References

SHOWING 1-10 OF 48 REFERENCES
Muscarinic m1 receptor-stimulated adenylate cyclase activity in Chinese hamster ovary cells is mediated by Gs alpha and is not a consequence of phosphoinositidase C activation.
TLDR
Results suggest that muscarinic agonist-stimulated cAMP accumulation in CHO-ml cells occurs via activation of Gs alpha and not as a consequence of phosphoinositidase C activation. Expand
Differential Effects of the M1–M5 Muscarinic Acetylcholine Receptor Subtypes on Intracellular Calcium and on the Incorporation of Choline Into Membrane Lipids in Genetically Modified Chinese Hamster Ovary Cell Lines
TLDR
Responses of Chinese hamster ovary cell lines stably transfected with human genes for the M1-M5 muscarinic receptor subtypes to several stimuli are compared and it appears likely that carbachol and ATP release Ca2+ ions from identical intracellular stores. Expand
Differential regulation of cAMP-mediated gene transcription by m1 and m4 muscarinic acetylcholine receptors. Preferential coupling of m4 receptors to Gi alpha-2.
TLDR
The m4 receptor is spontaneously active and can cause constitutive inhibition of adenylyl cyclase that is relieved by atropine treatment, and it is demonstrated that the Gi alpha-2 G-protein alpha subunit preferentially couples the m4 mAChR to inhibition of Adenylate cyclase in JEG-3 cells. Expand
Functional responses of cloned muscarinic receptors expressed in CHO-K1 cells.
TLDR
The physiological responses to activation of the m5 muscarinic acetylcholine receptor were compared with those of m3 and m4 in transformed Chinese hamster ovary cells, using patch-clamp electrophysiological and biochemical techniques, and indicate that each of the receptors has distinct functional properties. Expand
A novel mechanism for coupling of m4 muscarinic acetylcholine receptors to calmodulin-sensitive adenylyl cyclases: crossover from G protein-coupled inhibition to stimulation.
TLDR
A novel mechanism for muscarinic regulation of adenylyl cyclases that may involve crossover from inhibitory to stimulatory G protein coupling is demonstrated. Expand
Activation of adenylate cyclase by human recombinant sst5 receptors expressed in CHO‐K1 cells and involvement of Gαs proteins
TLDR
The data show that the sst5 receptor is very efficiently coupled in a negative manner to adenylate cyclase, however, at higher agonist concentrations the receptor can also mediate activation ofAdenylates cyclase by a mechanism apparently involving Gαs protein activation. Expand
Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: evidence for agonist-specific trafficking of intracellular responses.
TLDR
Findings demonstrate marked differences among cannabinoid receptor agonists in their activation of intracellular transduction pathways, providing support for the emerging concept of agonist-specific trafficking of cellular responses and further suggests strategies for developing receptors agonists with increased therapeutic utility. Expand
Activation of muscarinic acetylcholine receptors via their allosteric binding sites.
TLDR
It is found that the muscarinic receptor allosteric modulators alcuronium, gallamine, and strychnine alter the synthesis of cAMP in Chinese hamster ovary cells expressing the M2 or the M4 subtype ofMuscarinic receptors in the same direction as the agonist carbachol. Expand
Discrete activation of transduction pathways associated with acetylcholine m1 receptor by several muscarinic ligands.
TLDR
The ligand-selective cAMP accumulation, its independence from Ca2+ and the carbachol-activated adenylyl cyclase in membranes suggest that it represents an independent m1AChR-mediated signal, unrelated to phosphoinositide hydrolysis. Expand
Positive inotropic effects induced by carbachol in rat atria treated with islet‐activating protein (IAP) — association with phosphatidylinositol breakdown
  • S. Imai, H. Ohta
  • Chemistry, Medicine
  • British journal of pharmacology
  • 1988
TLDR
The results suggest that a muscarinic agonist such as carbachol can produce a positive inotropic effect in IAP‐treated atria, in association with PI breakdown, through activation of aMuscarinic receptor which shows some similarity to that previously identified in smooth muscles. Expand
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