Disease relevance of CHRM2

• The cellular localisation and the optical density of the immunoreactivity of the cholinergic enzyme choline acetyltransferase (CHAT-IR) and the muscarinic acetylcholine receptor m2 (m2-IR) in the medulla was described in 14 SIDS and 9 control cases [1].
• Proteolysis of the polypeptide chain of 64-amino-acid residues of hirudin HM2 by protease from Staphylococcus aureus V8, trypsin, thermolysin and subtilisin occurs at region 41-49 of the chain [2].
• A mutant of the human muscarinic acetylcholine receptor m2 subtype (m2 receptor), lacking a large part of the third intracellular loop, was expressed and purified using the baculovirus/insect cell culture system [3].
• To clarify the mechanisms of CNS toxicity following toluene exposure, especially with respect to the G protein-coupling of receptors, we determined the effects of toluene on the activation of Gi by stimulating human muscarinic acetylcholine receptor m2 subtypes (hm2 receptors) expressed in Chinese hamster ovary (CHO) cells [4].

Psychiatry related information on CHRM2

• We conclude that variation in CHRM2 predisposes to AD, DD and affective disorders [5].
• CHRM2 gene predisposes to alcohol dependence, drug dependence and affective disorders: results from an extended case-control structured association study [5].
• Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome [6].

High impact information on CHRM2

• We show that the HM2 and HM3 mAChRs efficiently inhibit adenylyl cyclase activity but poorly activate PI hydrolysis [7].
• One haplotype block within the 5'-UTR of CHRM2 may be more important for the development of these disorders than other regions [5].
• We examined 11 single nucleotide polymorphisms (SNPs) spanning the CHRM2 gene in these families [6].
• In this study, we evaluated whether genetic variation in the CHRM2 gene is also a risk factor for the correlated clinical characteristics of alcoholism and depression [6].
• The CHRM2 gene contains a single coding exon and a large 5' untranslated region encoded by multiple exons that can be alternatively spliced [6].

Biological context of CHRM2

• Using a combination of rapid amplification of 5' cDNA ends and reporter gene assays, we characterized the 5' untranslated region of the CHRM2 gene as expressed in human airway smooth muscle (HASM) cells [8].
• We also demonstrate significant linkage disequilibrium between CHRM2 SNPs and target case parietal delta band visual evoked oscillations (LD P<0.001) [9].
• Here we report significant linkage and linkage disequilibrium between target case frontal theta band, visual evoked brain oscillations and a single nucleotide polymorphism (SNP) from the cholinergic muscarinic receptor gene (CHRM2) on chromosome 7 [9].
• Down-regulation of muscarinic acetylcholine receptor M2 adversely affects the expression of Alzheimer's disease-relevant genes and proteins [10].
• These data suggest that DNA sequence variation at the CHRM2 locus is a potential modifier of HR recovery in the sedentary state and after short-term endurance training in healthy individuals [11].

Anatomical context of CHRM2

• Novel polymorphisms influencing transcription of the human CHRM2 gene in airway smooth muscle [8].
• Effects of toluene exposure on signal transduction: toluene reduced the signaling via stimulation of human muscarinic acetylcholine receptor m2 subtypes in CHO cells [4].

Associations of CHRM2 with chemical compounds

• We examined a common A-> T 1890 polymorphism in the 3' UTR of the cholinergic muscarinic receptor 2 (CHRM2) gene [12].
• Heart rate recovery after maximal exercise is associated with acetylcholine receptor M2 (CHRM2) gene polymorphism [11].
• In this view, we have synthesized an analogue of fragment 1-47 of hirudin HM2 in which Val1 has been replaced by tert-butylglycine, Ser2 by Arg, and Tyr3 by beta-naphthylalanine, to give the BugArgNal analogue [13].
• In the M2LKB2-2 cells, carbachol slightly stimulated the [3H]inositol monophosphate formation but had no significant effect in HM2-B10 cells [14].
• Palmitoylation of muscarinic acetylcholine receptor m2 subtypes: reduction in their ability to activate G proteins by mutation of a putative palmitoylation site, cysteine 457, in the carboxyl-terminal tail [15].

Other interactions of CHRM2

• When we compared the different passes, the intensity decreased in the following order: HM1, HMS, HM2, and HM3 [16].
• (d) Examination of family-based samples has identified several genes including GABRA2 and CHRM2 thought to be associated with alcohol dependence [17].
• Internalization and down-regulation of human muscarinic acetylcholine receptor m2 subtypes. Role of third intracellular m2 loop and G protein-coupled receptor kinase 2 [18].

Analytical, diagnostic and therapeutic context of CHRM2

• Linkage and linkage disequilibrium of evoked EEG oscillations with CHRM2 receptor gene polymorphisms: implications for human brain dynamics and cognition [9].
• Because acetylcholine receptor subtype M2 (CHRM2) plays a key role in the cardiac chronotropic response, we tested the hypothesis that, in healthy individuals, the CHRM2 gene polymorphisms might be associated with HR recovery 1 min after the termination of a maximal exercise test, both before and after endurance training [11].
• The diagnostic value of the PCR assay was evaluated in comparison to three other conventional H. meleagridis specific PCR tests (HIS5, HM1 and HM2) [19].
• Immunoblotting analyses revealed that the polyclonal antibody and four (HM1, HM2, HM3 and HM4) of five monoclonal antibodies reacted with myosin heavy chain [20].
• A putative palmitoylation site, Cys457, of muscarinic acetylcholine receptor m2 subtype (m2 receptor) was eliminated by conversion to alanine or stop codon by site-directed mutagenesis [15].

References