Molecule Information

General Information of the Molecule (ID: Mol02042)

• Name: Cholinergic receptor muscarinic 1 (CHRM1) ,Guinea-pig
• Synonyms: GPM1
• Molecule Type: Protein
• Gene Name: CHRM1
• Sequence:
  MNTSAPPAVSPNITILAPGKGPWQVAFIGITTGLLSLATVTGNLLVLISFKVNTELKTVN
  NYFLLSLACADLIIGTSSMNLYTTYLLMGHWALGTLACDLWLALDYVASNASVMNLLLIS
  FDRYFSVTRPLSYRTKRTPRRAALMIGLAWLVSFVLWAPAILFWQYLVGEQTVLAGQCYI
  QFLSQPIITFGTAMAAFYLPVTVMCALYWRIYRETENRARELAALQGSETPGKGGGSSSS
  SERSQPGAEGSPESPPGRCCRCCRAPRLLQAYSWKEEEEEDEGSMESLTSSEGEEPGSEV
  VIKMPMVDPEAQAPTKQPPRSSPNTVKRPTKKGRDRAGKGQKPRGKEQLAKRKTFSLVKE
  KKAARTLSAILLAFILTWTPYNIMVLVSTFCKDCVPETLWELGYWLCYVNSTINPMCYAL
  CNKAFRDTFRLLLLCRWDKRRWRKIPKRPGCLHRTPSR
• Function: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
• Uniprot ID: Q8VH28_CAVPO
• HGNC ID: HGNC:1950

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Rodentia
Family: Caviidae
Genus: Cavia
Species: .

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Dicyclomine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Asthma [ICD-11: CA23.0] [1]

• Sensitive Disease: Asthma [ICD-11: CA23.0]
• Sensitive Drug: Dicyclomine
• Molecule Alteration: Function; Inhibition
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Guinea-pig model; Cavia cutleri
• Experiment for Molecule Alteration: cAMP estimation analysis
• Mechanism Description: Dicyclomine, an antagonist of muscarinic receptors as well as an inhibitor of Ca++ ion influx, exhibited a similar pattern of inhibition with lower EC50 values against CCh when compared with high K+. In isolated guinea pig trachea, TS Oil inhibited carbachol (CCh, 1 M) and K+ (80 mM)-induced contractions in a pattern similar to that of dicyclomine. Methicillin-resistant S. aureus (MRSA) showed a small zone of inhibition as compared to standard strains (22 mm).

Docetaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [2]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MAPK signaling pathway; Activation; hsa04010
• In Vitro Model: 22Rv1DTXR cells; Prostate; Homo sapiens (Human); N.A.
• In Vitro Model: PC-3DTXR cells; Prostate; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell proliferation assay; Soft-agar colony formation assay; Tumorsphere formation assay
• Mechanism Description: Here, we demonstrate activation of the cholinergic muscarinic M1 receptor (CHRM1) in CRPC cells upon acquiring resistance to docetaxel, which is manifested in tumor tissues from PC patients post- vs. pre-docetaxel. Genetic and pharmacological inactivation of CHRM1 restores the efficacy of docetaxel in resistant cells. Mechanistically, CHRM1, via its first and third extracellular loops, interacts with the SEMA domain of cMET and forms a heteroreceptor complex with cMET, stimulating a downstream mitogen-activated protein polykinase program to confer docetaxel resistance.

References

• Ref 1: Possible Tracheal Relaxant and Antimicrobial Effects of the Essential Oil of Ethiopian Thyme Species (Thymus serrulatus Hochst. ex Benth.): A Multiple Mechanistic Approach .Front Pharmacol. 2021 Apr 5;12:615228. doi: 10.3389/fphar.2021.615228. eCollection 2021. 10.3389/fphar.2021.615228
• Ref 2: Cholinergic signaling via muscarinic M1 receptor confers resistance to docetaxel in prostate cancer. Cell Rep Med. 2024 Feb 20;5(2):101388.