Potential Role for Combined Subtype-Selective Targeting of M 1 and M 3 Muscarinic Receptors in Gastrointestinal and Liver Diseases.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical and mechanistic data with no primary clinical data.
PubMed 34803723 · doi:10.3389/fphar.2021.786105
What was done
Narrative mini-review examining the signaling pathways, divergent biological functions, and pharmacology of M1 and M3 muscarinic acetylcholine receptor subtypes (M1R and M3R). The authors synthesized preclinical evidence concerning their roles in gastrointestinal cancers (gastric, pancreatic, colon) and murine models of liver injury and fibrosis, while evaluating the availability and limitations of subtype-selective pharmacological agents.
What was found
The abstract reports no numerical data. Qualitatively, it highlights opposing downstream actions of the two Gq-coupled receptors: M3R activation promotes gastrointestinal neoplasia and accelerates murine liver fibrosis, whereas M1R activation demonstrates protective effects against GI neoplasia and mitigates liver fibrosis.
Why it matters
Clarifies the contrasting biological actions of structurally similar muscarinic receptors, highlighting a rationale for developing subtype-selective or combined M1R/M3R-targeting therapeutics for gastrointestinal and liver diseases.
Limits
As a narrative review, it lacks a systematic review methodology or meta-analytic quantification. Evidence is largely restricted to preclinical cellular mechanisms and murine models rather than clinical human data. No sample sizes or effect sizes are reported in the abstract.
Cited by
- supports Pirenzepine was developed by Boehringer Ingelheim as an oral drug for gastric ulcers that blocks acetylcholine-driven release of hydrochloric acid in the stomach.