CHRM3

CHRM3 Full Name

cholinergic receptor, muscarinic 3

CHRM3 Introduction

The muscarinic acetylcholine receptor M3 (M3) and its downstream effector Gq/11 have become key drug development targets due to their involvement in physiological and pathological processes. The muscarinic cholinergic receptors belong to a larger family of G protein coupled receptors. The functional diversity of these receptors is determined by the binding of acetylcholine, including adenylate cyclase inhibition, phosphoinositol denaturation, and potassium channel mediated cellular responses. The muscarinic receptors affect many functions of acetylcholine in the central and peripheral nervous systems. Muscatine cholinergic receptor 3 controls smooth muscle contraction, and its stimulation leads to secretion of glandular tissue. The use of selective promoters and alternative splicing result in multiple transcriptional variants with different tissue specificities.

Figure. Structure of CHRM3.

The muscarinic acetylcholine receptor M3 (M3 mAChR) is a member of the G protein coupled receptor superfamily, characterized by seven transmembrane domains and expressed in cardiomyocytes, stem cells, beta cells, neurons, smooth muscle cells, and various epithelial cells. Choline binds to M3 mAChR and regulates various pathophysiological processes, including cardiac injury, cardiac aging, cardiac fibrosis, cardiac hypertrophy (CH), immune regulation, and metabolic regulation.

Effect
Smooth Muscle
Due to the coupling of M3 receptor with Gq and mediation of intracellular calcium increase, it typically leads to smooth muscle contraction, such as the contraction observed during bronchial constriction. However, in terms of the vascular system, the activation of M3 on endothelial cells leads to an increase in nitric oxide synthesis, which diffuses to adjacent vascular smooth muscle cells and causes their relaxation and vasodilation, thus explaining the contradictory effects of parasympathetic nerve mimetics on vascular tension and bronchial tension.
Diabetes
Muscarinic M3 receptor regulates insulin secretion in the pancreas and is an important target for understanding the mechanism of type 2 diabetes. Some antipsychotic drugs (such as olanzapine and clozapine) used to treat schizophrenia and bipolar disorder have a high risk of diabetes side effects. These drugs can effectively bind to and block the muscarinic M3 receptor, which will lead to insulin imbalance and may lead to diabetes.

Alternate Names for CHRM3

CHRM3; cholinergic receptor, muscarinic 3; muscarinic acetylcholine receptor M3; cholinergic receptor, muscarinic 3, cardiac;