PMID:11714707

Citation	Takagi, N, Miyake-Takagi, K, Takagi, K, Tamura, H and Takeo, S (2002) Altered extracellular signal-regulated kinase signal transduction by the muscarinic acetylcholine and metabotropic glutamate receptors after cerebral ischemia. J. Biol. Chem. 277:6382-90
Abstract	To determine whether muscarinic acetylcholine receptors (mAChR) in the post-ischemic hippocampus may be involved in altered extracellular signal-regulated kinases (ERK) signal transduction, we have investigated changes in the activity of ERK1/2 induced by a muscarinic agonist, carbachol. Cerebral ischemia was produced in the rat by injecting 900 microspheres (48 microm in diameter) into the right internal carotid artery. Applying carbachol to the contralateral hippocampal slices from ischemic rats increased the phosphorylation of ERK1/2 but did not increase phosphorylation in the ipsilateral hippocampus. Analysis of M(1) mAChR binding showed that there was no significant difference in the number and K(d) values between the hippocampi from naïve and ischemic rats. Immunoblotting analysis showed no significant difference in the amount of M(1) mAChR in both hemispheres. In contrast to carbachol stimulation, the protein kinase C activator induced an activation of ERK1/2 in the ipsilateral hippocampus. This increase was shown to occur in neurons by immunofluorescence colocalization study. Carbachol-stimulated tyrosine phosphorylation of the G alpha(q/11), inositol 1,4,5-trisphosphate formation, and association of G alpha(q/11) with phospholipase C beta 1 were attenuated in the ipsilateral hippocampus. We also found that stimulation of group I metabotropic glutamate receptors, which are linked to G alpha(q/11), failed to increase in phosphorylation of ERK1/2 in the ipsilateral hippocampus. These results suggest that failure in receptor-mediated tyrosine phosphorylation of the G alpha(q/11) subunit and a defect in receptor-G alpha(q/11-)effector coupling in the ischemic hippocampus may be involved in alterations of ERK signal transduction.
Links	PubMed Online version:10.1074/jbc.M108081200
Keywords	Animals; Atropine/pharmacology; Brain Ischemia/physiopathology; Carbachol/pharmacology; Functional Laterality; Hippocampus/physiopathology; Intracranial Embolism/physiopathology; Kinetics; MAP Kinase Signaling System/physiology; Male; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases/metabolism; Phosphorylation; Rats; Rats, Wistar; Receptor, Muscarinic M1; Receptors, Metabotropic Glutamate/physiology; Receptors, Muscarinic/physiology; Reference Values; Signal Transduction/physiology; Tetradecanoylphorbol Acetate/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:MK01	involved_in	GO:0007165: signal transduction	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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