Elucidating the role of muscarinic receptors in psychosis

Felder, Christian C.; Porter, Amy C.; Skillman, Tiffanie L.; Zhang, Lu; Bymaster, Frank P.; Nathanson, Neil M.; Hamilton, Susan; Gomeza, Jesús; Wess, Jürgen; McKinzie, David L.

doi:10.1016/s0024-3205(01)01059-1

Cited by 108 publications

(84 citation statements)

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“…These findings support the hypothesis that drugs which target specific muscarinic receptors will be beneficial in treating the symptoms of schizophrenia. 29,30 Further investigations of changes in specific muscarinic receptors in a larger number of cortical regions will be required to fully determine the regional specificity of changes in muscarinic receptors in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia

et al. 2002

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To test the hypothesis that muscarinic receptors are involved in the pathology of schizophrenia, we measured muscarinic 1 (M1R) and muscarinic 4 (M4R) protein and mRNA as well as [ 3 H]pirenzepine binding in Brodmann's areas (BA) 9 and 40 obtained postmortem from 20 schizophrenic and 20 age/sex-matched control subjects. There was a significant decrease in [ 3 H]pirenzepine binding to BA 9 (mean ± SEM: 151 ± 15 vs 195 ± 10 fmol mg −1 ETE; P Ͻ 0.02), but not BA 40 (143 ± 13 vs 166 ± 11 fmol mg −1 ETE), from subjects with schizophrenia. The level of M1R protein (0.11 ± 0.007 vs 0.15 ± 0.008 OD; P Ͻ 0.01), but not M4R protein, was decreased in BA9 from schizophrenic subjects with neither receptor protein being altered in BA 40. The level of M1R mRNA was decreased in BA 9 (30 ± 7.0 vs 79 ± 14 dpm × 10 3 mg −1 ETE, P Ͻ 0.01) and BA 40 (28 ± 5.9 vs 99 ± 14, P Ͻ 0.01) with schizophrenia but M4R mRNA was only decreased in BA 40 (48 ± 6.6 vs 89 ± 9.9, P Ͻ 0.005). These data suggest that the M1R, at least in the dorsolateral prefrontal cortex, may have a role in the pathology of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia

et al. 2002

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“…Behavioral and neurochemical analysis of M 4 receptor knock-out mice has shown that the M 4 mAChR plays an important role in the dopamine homeostasis, especially in striatal areas (Gomeza et al, 1999;Felder et al, 2001;Zhang et al, 2002;Tzavara et al, 2004;Fink-Jensen et al, 2011). The M 4 mAChR subtype is the major mAChR expressed in the striatum (Levey, 1993), where the receptor is expressed on cholinergic interneurons, as well as on GABAergic projection neurons, where it is coexpressed with D 1 dopamine receptors (Weiner et al, 1990;Bernard et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Involvement of a Subpopulation of Neuronal M₄Muscarinic Acetylcholine Receptors in the Antipsychotic-like Effects of the M₁/M₄Preferring Muscarinic Receptor Agonist Xanomeline

Dencker¹,

Wörtwein²,

Weikop³

et al. 2011

J. Neurosci.

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“…The M1, M2, and M4 receptors are the most abundant. The M1 receptor is found in the hippocampal and cortical regions of the brain as well as in the parasympathetic ganglia 2,3,4 . The M1 receptor is involved in many processes, including the initiation of seizures, learning and memory, and regulation of the force and rate of heart contractions 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms of the human M1 muscarinic acetylcholine receptor gene

2001

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The gene encoding the human muscarinic receptor, type 1 (CHRM1), was genotyped from 245 samples of the Coriell Collection (Coriell Institute for Medical Research, Camden, NJ). Fifteen single nucleotide polymorphisms (SNPs) were discovered, 9 of which are located in the coding region of the receptor. Of these, 8 represent synonymous SNPs, indicating that CHRM1 is highly conserved in humans. Only a single allele was found to contain a nonsynonymous SNP, which encodes an amino acid change of Cys to Arg at position 417. This may have functional consequences because a C417S point mutation in rat M1 was previo usly shown to affect receptor binding and coupling. Furthermore, 0 of 4 SNPs within CHRM1 previously deduced from sequencing of the human genome were found in this study despite a prediction that a majority of such inferred SNPs are accurate. The consensus sequence of CHRM1 obtained in our study differs from the deposited reference sequence (AC NM_000738) in 2 adjacent nucleotides, leading to a V173M change, suggesting a sequencing error in the reference sequence. The extraordinary sequence conservation of the CHRM1 gene-coding region was unexpected as M1-knockout mice show only minimal functional impairments.

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Elucidating the role of muscarinic receptors in psychosis

Cited by 108 publications

References 0 publications

Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia

Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia

Involvement of a Subpopulation of Neuronal M₄Muscarinic Acetylcholine Receptors in the Antipsychotic-like Effects of the M₁/M₄Preferring Muscarinic Receptor Agonist Xanomeline

Single nucleotide polymorphisms of the human M1 muscarinic acetylcholine receptor gene

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Elucidating the role of muscarinic receptors in psychosis

Cited by 108 publications

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Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia

Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia

Involvement of a Subpopulation of Neuronal M4Muscarinic Acetylcholine Receptors in the Antipsychotic-like Effects of the M1/M4Preferring Muscarinic Receptor Agonist Xanomeline

Single nucleotide polymorphisms of the human M1 muscarinic acetylcholine receptor gene

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Involvement of a Subpopulation of Neuronal M₄Muscarinic Acetylcholine Receptors in the Antipsychotic-like Effects of the M₁/M₄Preferring Muscarinic Receptor Agonist Xanomeline