Overview
- Peptide (C)HNATTVNGTPVNHQPLER, corresponding to amino acid residues 7-24 of human M5 muscarinic receptor (Accession P08912). Extracellular, N-terminus.
- Rat brain and lung membranes, A-875 human melanoma and MALM-3M human malignant melanoma.
Western blot analysis of rat lung (lanes 1 and 5) and brain (lanes 2 and 6) membranes, human A-875 melanoma (lanes 3 and 7) and human MALM-3M malignant melanoma (lanes 4 and 8) cell lysates:1-4. Anti-CHRM5 (extracellular) Antibody (#AMR-005), (1:200).
5-8. Anti-CHRM5 (extracellular) Antibody, preincubated with CHRM5 (extracellular) Blocking Peptide (#BLP-MR005).
Acetylcholine is a neurotransmitter which activates two different groups of receptors: nicotinic acetylcholine receptors (nAChR) which belong to the superfamily of ligand-gated ion channels, and muscarinic acetylcholine receptors (mAChR) which belong to the G-protein coupled receptor (GPCR) superfamily. There are five separate gene products (M1-M5) that, assembled, make up this GPCR subfamily and like all GPCRs, have seven transmembrane spanning domains.
Generally, M1, M3 and M5 muscarinic receptors are known to activate phospholipase C (PLC) via Gq coupling, while M2 and M4 muscarinic receptors couple to Gi/o, and therefore inhibit adenylate cyclase1. This classification is however not clear cut.
mAChR can activate adenylate cyclase by coupling to Gs2. In addition, M2 and M4 muscarinic receptors, when overexpressed, can also activate adenylate cyclase in some systems3-5.
Evidence suggests that muscarinic receptors can form homo- or heterodimers and that the dimer formed can subsequently affect the downstream signaling pathways1.
Muscarinic receptors have been shown to regulate voltage-gated Ca2+ channels, namely CaV2.16, as well acid sensing ion channels (ASIC)7. Generally speaking, the actions of muscarinic receptors on ion channels can be either via 2nd messengers or through their direct action on the channels once activated8.
Furthermore, muscarinic receptors can also promote endocytosis of ion channels (KV1.2 for example) by recruiting tyrosine kinases that phosphorylate the channel in order to terminate its activity9. Other diverse and important functions of muscarinic receptors include cell growth, survival and physiology1.
Expression of muscarinic receptors is found in neurons in the central nervous system as well as in the peripheral nervous system. These receptors are also expressed in cardiac and smooth muscle, lung, intestine, ovary and urothelium1,10.
The M5 muscarinic receptor has been the most difficult receptor to study as there is no specific pharmacology targeted against the receptor and no high level of expression has been detected in tissues. However, the effects of single knockout mice were studied and it was observed that in M5 knockouts there is a moderate decrease in ligand binding in the lung and bladder, two organs expressing the M5 muscarinic receptor11. In addition, it has been proposed that the M5 muscarinic receptor may be involved in interstitial cystitis, a urinary bladder disorder12.
