InterPro: IPR001065 Muscarinic acetylcholine receptor M2

G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [1]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs: http://www.gpcr.org/7tm/.

The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [2, 3, 4].

The muscarinic acetylcholine receptors, present in the central nervous system, spinal cord motoneurons and autonomic preganglia, modulate a variety of physiological functions: these include airway, eye and intestinal smooth muscle contractions; heart rate; and glandular secretions. The receptors mediate adenylate cyclase attenuation, calcium and potassium channel activation, and phosphatidyl inositol turnover [5]. This diversity may result from the occurrence of multiple receptor subtypes, which have been classified based on observed differences in ligand binding to receptors in membranes from several tissues.

The M2 receptor is found in low levels in the CNS, where it has a limited distribution. By contrast, M2 receptors are expressed in high density in the heart, where they induce a decrease in inotropy and bradycardia. They are also found in smooth muscle. No selective agonist has been described [6].