mAChRs

mAChRs, or muscarinic acetylcholine receptors, are a class of G protein-coupled receptors (GPCRs) that are activated by the neurotransmitter acetylcholine. These receptors play a crucial role in the parasympathetic nervous system, mediating various physiological responses including modulation of heart rate, smooth muscle contraction, glandular secretion, and cognitive functions.

There are five subtypes of mAChRs, labeled M1 through M5, each encoded by distinct genes and exhibiting different tissue distributions and functional properties. M1, M3, and M5 are generally coupled to Gq proteins, leading to the activation of phospholipase C, increased intracellular calcium levels, and subsequent cellular responses. Conversely, M2 and M4 are coupled to Gi/o proteins, which inhibit adenylate cyclase activity, reducing cyclic AMP levels and modulating cellular activity accordingly.

mAChRs are widely expressed throughout the body. For example, M2 receptors are predominant in cardiac tissue, where they help regulate heart rate. M3 receptors are found in smooth muscles and glands, contributing to responses such as bronchoconstriction and salivation. In the central nervous system, mAChRs influence cognition, memory, and neuroplasticity.

Pharmacologically, mAChRs are targeted by various drugs used to treat conditions like glaucoma, gastrointestinal disorders, and motion sickness. Muscarinic agonists activate these receptors, while antagonists block them, impacting parasympathetic signaling.

Research on mAChRs continues to provide insights into their role in health and disease, including neurodegenerative diseases like Alzheimer's, where cholinergic signaling is impaired. Understanding the diverse functions and mechanisms of mAChRs remains vital for developing targeted therapies.