A metabotropic receptor, also referred to by the broader term G-protein-coupled receptor, is a type of membrane receptor that initiates a number of metabolic steps to modulate cell activity. The nervous system utilizes two types of receptors: metabotropic and ionotropic receptors. While ionotropic receptors form an ion channel pore, metabotropic receptors are indirectly linked with ion channels through signal transduction mechanisms, such as G proteins. Both receptor types are activated by specific chemical ligands. When an ionotropic receptor is activated, it opens a channel that allows ions such as Na+, K+, or Cl− 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 of second messenger chemicals. Chemical messengers bind to metabotropic receptors to initiate a diversity of effects caused by biochemical signaling cascades. G protein-coupled receptors are all metabotropic receptors. When a ligand binds to a G protein-coupled receptor, a guanine nucleotide-binding protein, or G protein, activates a second messenger cascade which can alter gene transcription, regulate other proteins in the cell, release intracellular Ca2+, or directly affect ion channels on the membrane. 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. Metabotropic receptors have a diversity of ligands, including but not limited to: small molecule transmitters, monoamines, peptides, hormones, and even gases. In comparison to fast-acting neurotransmitters, these ligands are not taken up again or degraded quickly. They can also enter the circulatory system to globalize a signal. Most metabotropic ligands have unique receptors. Some examples include: metabotropic glutamate receptors, muscarinic acetylcholine receptors, GABAB receptors.

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