Inhibition of Basal and Amphetamine-stimulated Extracellular Signal-regulated Kinase (ERK) Phosphorylation in the Rat Forebrain by Muscarinic Acetylcholine M4 Receptors

Overview

Journal Brain Res

Specialty Neurology

Date 2018 Mar 27

PMID 29577888

Citations 1

Authors

Nan He

Li-Min Mao

Adrian W Sturich

Dao-Zhong Jin

John Q Wang

Affiliations

Soon will be listed here.

Abstract

The mitogen-activated protein kinase (MAPK), especially its extracellular signal-regulated kinase (ERK) subfamily, is a group of kinases enriched in the mammalian brain. While ERK is central to cell signaling and neural activities, the regulation of ERK by transmitters is poorly understood. In this study, the role of acetylcholine in the regulation of ERK was investigated in adult rat striatum in vivo. We focused on muscarinic M1 and M4 receptors, two principal muscarinic acetylcholine (mACh) receptor subtypes in the striatum. A systemic injection of the M1-preferring antagonist telenzepine did not alter ERK phosphorylation in the two subdivisions of the striatum, the caudate putamen and nucleus accumbens. Similarly, telenzepine did not affect ERK phosphorylation in the medial prefrontal cortex (mPFC), hippocampus, and cerebellum. Moreover, telenzepine had no effect on the ERK phosphorylation induced by dopamine stimulation with the psychostimulant amphetamine. In contrast to telenzepine, the M4-preferring antagonist tropicamide consistently increased ERK phosphorylation in the striatum and mPFC. This increase was rapid and transient. Tropicamide and amphetamine when coadministered at subthreshold doses induced a significant increase in ERK phosphorylation. These results demonstrate that mACh receptors exert a subtype-specific modulation of ERK in striatal and mPFC neurons. While the M1 receptor antagonist has no effect on ERK phosphorylation, M4 receptors inhibit constitutive and dopamine-stimulated ERK phosphorylation in these dopamine-innervated brain regions.

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References

Volmat V, Pouyssegur J . Spatiotemporal regulation of the p42/p44 MAPK pathway. Biol Cell. 2001; 93(1-2):71-9. DOI: 10.1016/s0248-4900(01)01129-7. View

Shi X, McGinty J . D1 and D2 dopamine receptors differentially mediate the activation of phosphoproteins in the striatum of amphetamine-sensitized rats. Psychopharmacology (Berl). 2010; 214(3):653-63. PMC: 3065836. DOI: 10.1007/s00213-010-2068-4. View

Thomas G, Huganir R . MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci. 2004; 5(3):173-83. DOI: 10.1038/nrn1346. View

Pearson G, Robinson F, Beers Gibson T, Xu B, Karandikar M, Berman K . Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001; 22(2):153-83. DOI: 10.1210/edrv.22.2.0428. View

Dencker D, Weikop P, Sorensen G, Woldbye D, Wortwein G, Wess J . An allosteric enhancer of M₄ muscarinic acetylcholine receptor function inhibits behavioral and neurochemical effects of cocaine. Psychopharmacology (Berl). 2012; 224(2):277-87. PMC: 3914671. DOI: 10.1007/s00213-012-2751-8. View

Eltze M, Gonne S, Riedel R, Schlotke B, Schudt C, Simon W . Pharmacological evidence for selective inhibition of gastric acid secretion by telenzepine, a new antimuscarinic drug. Eur J Pharmacol. 1985; 112(2):211-24. DOI: 10.1016/0014-2999(85)90498-4. View

Chapman K, Vaswani D, Hendry N, Langmead C, Kew J, Watson J . The muscarinic M(4) receptor is the functionally predominant subtype in rat and mouse striatum as demonstrated using [(35)S] GTPγS binding. Eur J Pharmacol. 2010; 652(1-3):1-6. DOI: 10.1016/j.ejphar.2010.10.079. View

Hersch S, Gutekunst C, Rees H, Heilman C, Levey A . Distribution of m1-m4 muscarinic receptor proteins in the rat striatum: light and electron microscopic immunocytochemistry using subtype-specific antibodies. J Neurosci. 1994; 14(5 Pt 2):3351-63. PMC: 6577507. View

Bertran-Gonzalez J, Bosch C, Maroteaux M, Matamales M, Herve D, Valjent E . Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. J Neurosci. 2008; 28(22):5671-85. PMC: 6670792. DOI: 10.1523/JNEUROSCI.1039-08.2008. View

10.

Jeon J, Dencker D, Wortwein G, Woldbye D, Cui Y, Davis A . A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors. J Neurosci. 2010; 30(6):2396-405. PMC: 2824442. DOI: 10.1523/JNEUROSCI.3843-09.2010. View

11.

Betz A, McLaughlin P, Burgos M, Weber S, Salamone J . The muscarinic receptor antagonist tropicamide suppresses tremulous jaw movements in a rodent model of parkinsonian tremor: possible role of M4 receptors. Psychopharmacology (Berl). 2007; 194(3):347-59. DOI: 10.1007/s00213-007-0844-6. View

12.

Mao L, Reusch J, Fibuch E, Liu Z, Wang J . Amphetamine increases phosphorylation of MAPK/ERK at synaptic sites in the rat striatum and medial prefrontal cortex. Brain Res. 2012; 1494:101-8. PMC: 3546198. DOI: 10.1016/j.brainres.2012.11.038. View

13.

Yasuda R, Ciesla W, FLORES L, Wall S, Li M, Satkus S . Development of antisera selective for m4 and m5 muscarinic cholinergic receptors: distribution of m4 and m5 receptors in rat brain. Mol Pharmacol. 1993; 43(2):149-57. View

14.

Wang J, Fibuch E, Mao L . Regulation of mitogen-activated protein kinases by glutamate receptors. J Neurochem. 2006; 100(1):1-11. DOI: 10.1111/j.1471-4159.2006.04208.x. View

15.

Joseph L, Thomsen M . Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M, M, and M receptor knockout mice. Behav Brain Res. 2017; 329:75-83. PMC: 5495997. DOI: 10.1016/j.bbr.2017.04.023. View

16.

Lazareno S, Buckley N, ROBERTS F . Characterization of muscarinic M4 binding sites in rabbit lung, chicken heart, and NG108-15 cells. Mol Pharmacol. 1990; 38(6):805-15. View

17.

Sweatt J . Mitogen-activated protein kinases in synaptic plasticity and memory. Curr Opin Neurobiol. 2004; 14(3):311-7. DOI: 10.1016/j.conb.2004.04.001. View

18.

Li Z, Huang M, Ichikawa J, Dai J, Meltzer H . N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarinic receptors. Neuropsychopharmacology. 2005; 30(11):1986-95. DOI: 10.1038/sj.npp.1300768. View

19.

Wess J . Molecular biology of muscarinic acetylcholine receptors. Crit Rev Neurobiol. 1996; 10(1):69-99. DOI: 10.1615/critrevneurobiol.v10.i1.40. View

20.

Caulfield M, Birdsall N . International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev. 1998; 50(2):279-90. View