M3 receptor

The M3 muscarinic acetylcholine receptor is a type of muscarinic acetylcholine receptor that is primarily found in the smooth muscle and glandular tissue of the body. It is one of the five subtypes of muscarinic receptors, which are part of the larger family of G protein-coupled receptors (GPCRs). The M3 receptor plays a crucial role in various physiological processes, including the regulation of smooth muscle contraction, glandular secretion, and certain central nervous system functions.

Structure

The M3 receptor is a G protein-coupled receptor that spans the cell membrane seven times, a characteristic feature of GPCRs. It is encoded by the CHRM3 gene in humans. The receptor is composed of an extracellular N-terminus, seven transmembrane alpha-helices, three extracellular loops, three intracellular loops, and an intracellular C-terminus. The binding of acetylcholine to the M3 receptor induces a conformational change that activates the associated G protein.

Function

The primary function of the M3 receptor is to mediate the effects of the neurotransmitter acetylcholine in various tissues. Upon activation by acetylcholine, the M3 receptor couples with the Gq protein, leading to the activation of phospholipase C (PLC). This enzyme catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 stimulates the release of calcium ions from the endoplasmic reticulum, while DAG activates protein kinase C (PKC). These signaling pathways result in various cellular responses, such as smooth muscle contraction and increased glandular secretion.

Physiological Roles

The M3 receptor is involved in several physiological processes:

• Smooth Muscle Contraction: The M3 receptor is responsible for mediating the contraction of smooth muscles in the gastrointestinal tract, bronchi, and bladder.
• Glandular Secretion: It stimulates the secretion of saliva, sweat, and other glandular secretions.
• Eye Function: In the eye, the M3 receptor mediates the contraction of the ciliary muscle and the sphincter pupillae, affecting accommodation and pupil constriction.
• Central Nervous System: Although less prominent, the M3 receptor is also expressed in the central nervous system, where it may play a role in cognitive functions and memory.

Clinical Significance

The M3 receptor is a target for various pharmacological agents. Antagonists of the M3 receptor, such as ipratropium and tiotropium, are used in the treatment of chronic obstructive pulmonary disease (COPD) and asthma to relax bronchial smooth muscle and reduce airway resistance. Agonists of the M3 receptor are less commonly used but may have potential therapeutic applications in conditions requiring increased smooth muscle contraction or glandular secretion.

Research and Development

Ongoing research is focused on developing selective M3 receptor modulators that can provide therapeutic benefits with minimal side effects. Understanding the precise role of the M3 receptor in various diseases could lead to the development of novel treatments for conditions such as overactive bladder, xerostomia, and certain neurological disorders.

Also see

• Muscarinic acetylcholine receptor
• G protein-coupled receptor
• Acetylcholine
• Smooth muscle
• Chronic obstructive pulmonary disease