Metabotropic receptor

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A metabotropic 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.[1]


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.[2][3] 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.[4]

Metabotropic receptors have a diversity of ligands, including but not limited to: small molecule transmitters, monoamines, peptides, hormones, and even gases.[4][5][6] 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.[2] Most metabotropic ligands have unique receptors. Some examples include: metabotropic glutamate receptors, muscarinic acetylcholine receptors, GABAB receptors.[1][7]


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's N terminus is located on the extracellular side of the membrane and its C terminus is on the intracellular side.[1]

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 ~ 450-550 amino acids.


  1. ^ a b c Williams, S. J.; Purves, Dale (2001). Neuroscience. Sunderland, Mass: Sinauer Associates. ISBN 0-87893-742-0.
  2. ^ a b "Principles of Neural Design", The MIT Press, 2015, doi:10.7551/mitpress/9395.003.0019, ISBN 978-0-262-32731-2, retrieved October 18, 2020 Missing or empty |title= (help)
  3. ^ Ferguson, Duncan C. (January 1, 2018), Wallig, Matthew A.; Haschek, Wanda M.; Rousseaux, Colin G.; Bolon, Brad (eds.), "Chapter 4 - Principles of Pharmacodynamics and Toxicodynamics", Fundamentals of Toxicologic Pathology (Third Edition), Academic Press, pp. 47–58, doi:10.1016/b978-0-12-809841-7.00004-6, ISBN 978-0-12-809841-7, retrieved October 30, 2020
  4. ^ a b Nadim, Farzan; Bucher, Dirk (December 2014). "Neuromodulation of Neurons and Synapses". Current Opinion in Neurobiology. 0: 48–56. doi:10.1016/j.conb.2014.05.003. ISSN 0959-4388. PMC 4252488. PMID 24907657.
  5. ^ Burrows, Malcolm (1996). "Neurotransmitters, neuromodulators and neurohormones". The Neurobiology of an Insect Brain. Oxford Scholarship. doi:10.1093/acprof:oso/9780198523444.003.0005. ISBN 9780198523444.
  6. ^ Marder, Eve (October 4, 2012). "Neuromodulation of Neuronal Circuits: Back to the Future". Neuron. 76 (1): 1–11. doi:10.1016/j.neuron.2012.09.010. ISSN 0896-6273. PMC 3482119. PMID 23040802.
  7. ^ Hoehn K, Marieb EN (2007). "Fundamentals of the nervous system and nervous tissue". Human Anatomy & Physiology. San Francisco: Pearson Benjamin Cummings. ISBN 978-0-8053-5910-7.

Further reading[edit]

  • Zimmerberg, B. 2002. Dopamine receptors: A representative family of metabotropic receptors. Multimedia Neuroscience Education Project [1]