Distribution and function of the muscarinic receptor subtypes in the cardiovascular system

Abstract

Muscarinic acetylcholine receptors belong to the G protein-coupled receptor superfamily and are widely known to mediate numerous functions within the central and peripheral nervous system. Thus, they have become attractive therapeutic targets for various disorders. It has long been known that the parasympathetic system, governed by acetylcholine, plays an essential role in regulating cardiovascular function. Unfortunately, due to the lack of pharmacologic selectivity for any one muscarinic receptor, there was a minimal understanding of their distribution and function within this region. However, in recent years, advancements in research have led to the generation of knockout animal models, better antibodies, and more selective ligands enabling a more thorough understanding of the unique role muscarinic receptors play in the cardiovascular system. These advances have shown muscarinic receptor 2 is no longer the only functional subtype found within the heart and muscarinic receptors 1 and 3 mediate both dilation and constriction in the vasculature. Although muscarinic receptors 4 and 5 are still not well characterized in the cardiovascular system, the recent generation of knockout animal models will hopefully generate a better understanding of their function. This mini review aims to summarize recent findings and advances of muscarinic involvement in the cardiovascular system.