Ametabotropic receptor, also referred to by the broader termG-protein-coupled receptor,[1] is a type of membrane receptor that initiates a number ofmetabolic steps to modulate cell activity. Thenervous system utilizes two types ofreceptors:metabotropic andionotropic receptors. While ionotropic receptors form anion channel pore, metabotropic receptors are indirectly linked with ion channels through signal transduction mechanisms, such asG proteins. These two types of receptors, along with their number and activity level, form the basis of thesympathetic andparasympathetic nervous systems and play key roles in regulating rates of resting energy expenditure (REE), resting heart rate, heart rate variability, and global myocardial oxygen consumption.
Both receptor types are activated by specificchemical ligands. When an ionotropic receptor is activated, it opens a channel that allows ions such asNa+,K+, orCl− to flow. In contrast, when a metabotropic receptor is activated, a series of intracellular events are triggered that can also result in ion channels opening or other intracellular events, but involve a range ofsecond messenger chemicals.[2]
Chemical messengers bind to metabotropic receptors to initiate a diversity of effects caused by biochemicalsignaling cascades. G protein-coupled receptors are all metabotropic receptors. When a ligand binds to a G protein-coupled receptor, aguanine nucleotide-binding protein, orG protein, activates a second messenger cascade which can altergene transcription, regulate other proteins in the cell, releaseintracellular Ca2+, or directly affect ion channels on the membrane.[3][4] These receptors can remain open from seconds to minutes and are associated with long-lasting effects, such as modifying synaptic strength and modulating short- and long-term synaptic plasticity.[5]
Metabotropic receptors have a diversity of ligands, including but not limited to: small molecule transmitters,monoamines,peptides,hormones, and even gases.[5][6][7] In comparison to fast-actingneurotransmitters, these ligands are not taken up again or degraded quickly. They can also enter thecirculatory system to globalize a signal.[3] Most metabotropic ligands have unique receptors. Some examples include:metabotropic glutamate receptors,muscarinic acetylcholine receptors,GABAB receptors.[2][8]
The G protein-coupled receptors have seven hydrophobic transmembrane domains. Most of them are monomeric proteins, although GABAB receptors require heterodimerization to function properly. The protein'sN terminus is located on the extracellular side of the membrane and its C terminus is on the intracellular side.[2]
The 7 transmembrane spanning domains, with an external amino terminus, are often claimed as being alpha helix shaped, and the polypeptide chain is said to be composed of around 450–550 amino acids.
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