CHRM1 Membrane Protein Introduction

Introduction of CHRM1

CHRM1, encoded by CHRM1 gene, is a member of G protein-coupled receptors family. It is coupled with G proteins of class G_q and possesses seven transmembrane domain. The protein is a muscarinic receptor that is used as a therapeutic target for treatment of Alzheimer disease. And many therapeutic drugs and other substances are made by selecting CHRM1 as agonists or antagonists.

Function of CHRM1 Membrane Protein

CHRM1 functions by the binding of acetylcholine and is involved in a lot of cellular responses. It can inhibit adenylate cyclase, degenerate phosphoinositide, and mediate potassium channel. Moreover, muscarinic acetylcholine receptor can regulate acetylcholine activities in both the central nervous system (CNS) and the periphery involving in a lot of organism metabolic processes. For example, the acetylcholine activation in the periphery can increase exocrine secretions from sweat and lacrimal glands, promote the contraction of smooth muscle in the gastrointestinal tract, airways, ciliary body, and iris sphincter, reduce heart rate and vasodilatation of vascular beds. CHRM1, one of the five muscarinic receptors subtypes, enables to regulate vagally-induced bronchoconstriction and the acid secretion of the gastrointestinal tract. Moreover, CHRM1 regulates oxidative stress response to acute liver injury induced by acetaminophen, and treatment of murine AML12 hepatocytes with a CHRM1 antagonist could relieve H₂O₂-induced oxidative stress, prevented GSH depletion, and enhanced viability. In addition, CHRM1 is associated with the progression of multiple diseases, such as Alzheimer disease, Huntington's disease, as well as asthma.

Fig.1 Acetylcholine binds to CHRM1.

Application of CHRM1 Membrane Protein in Literature

1. Bradley S J., et al. Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes. Molecular Pharmacology. 2018, 93(6): 645-656. PubMed ID: 29695609
   
   

   It was proved that bitopic binding mode of a CHRM1 agonist could alleviate cognitive dysfunction in Alzheimer's disease patients. But CHRM1 agonist treatment also induces significant side-effects. So it is not desirable for a clinical candidate due to the likelihood of adverse side effects.

2. Kevin S., et al. Effects of muscarinic M 1, and M 4, acetylcholine receptor stimulation on extinction and reinstatement of cocaine seeking in male mice, independent of extinction learning. Psychopharmacology. 2018, 235(3): 815-827. PubMed ID: 29250738
   
   

   The study shows that CHRM1/CHRM4 stimulation can decrease cocaine seeking in mice. It also suggests that CHRM1/CHRM4 stimulation may mediate or reverse some neurochemical effects of cocaine exposure.

3. Neuhofer D., et al. Muscarinic M1 Receptor Modulation of Synaptic Plasticity in Nucleus Accumbens of Wild-Type and Fragile X Mice. ACS Chemical Neuroscience. 2018, 9(9): 2233-2240. PubMed ID: 29486555
   
   

   The study reveals the complex influence of acetylcholine on excitatory synapses in the nucleus accumbens core and identifies new substrates of the synaptic deficits of Fragile X.

4. Lópezramírez Y L., et al. Muscarinic Receptors Types 1 and 2 in the Preoptic-Anterior Hypothalamic Areas Regulate Ovulation Unequally in the Rat Oestrous Cycle. International Journal of Endocrinology. 2017, 2017(9): 1-9. PubMed ID: 28396684
   
   

   The study was designed to count muscarinic receptors types 1 and 2 in the preoptic and anterior hypothalamus areas (POA-AHA) and analyze the effects of blocking these receptors on spontaneous ovulation. The result suggests that m1AChR or m2AChR in the POA-AHA could participate in the regulation of spontaneous ovulation in rats.

5. Cropley V L., et al. The effect of a muscarinic receptor 1 gene variant on grey matter volume in schizophrenia. Psychiatry Research Neuroimaging. 2015, 234(2): 182-187. PubMed ID: 26481978
   
   

   The study suggests that the SNP c.267C>A within the CHRM1 is associated with brain structure in the right precentral gyrus in individuals with schizophrenia/schizoaffective disorder. Individuals with homozygous (267C/C) significantly reduced grey matter volume (GMV) in the right precentral gyrus compared to those with heterozygous (267C/A).

CHRM1 Preparation Options

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