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Down-regulation and Upregulation of Receptors - Overview

Down-regulation of receptor happens when receptors have been chronically exposed to excessive amount of neurotransmitters, endogenous and/or drugs. It results ligand-induced desensitization of that receptors or ligand-induced internalization. It is usually exhibited by various hormone receptors. ^[1] Up-regulation of receptors, on the other hand, results super-sensitized receptors especially after repeated exposure to the drug ^[2].

Insulin Receptor Down-regulation Mechanism

The process of downregulation occurs when there are elevated levels of the hormone insulin in the blood^[3]. When insulin binds to its receptors on the surface of a cell, the hormone receptor complex undergoes endocytosis and is subsequently attacked by intracellular lysosomal enzymes^[4]. The internalization of the insulin molecules provides a pathway for degradation of the hormone as well as for regulation of the number of sites that are available for binding on the cell surface. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of synthesis of new receptors within the endoplasmic reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell’s sensitivity to the elevated hormone concentration. The process of decreasing the number of receptor sites is virtually the same for all hormones; it varies only in the receptor hormone complex.

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Downregulation and upregulation

Even though the title of this page contains both downregulation and upregulation, the page only discusses about Downregulation. I would love to add some information of upregulation of receptors as well as changing the title to "Downregulation and Upregulation of receptors", because the page only is discussing about receptor downregulation.

In this page, there is a section named "Insulin receptor mechanism" which seems to be discussing about insulin receptor downregulation. The section name should be "insulin receptor downregulation mechanism". Under the "Insulin receptor mechanism", there is a section named "reversal". I think it should be discussed under upregulation, or be deleted. The way the section is written is too suggestive, more sounds like healthier life style suggestions, than explaining how 'reversal' happens in scientific terms.

In addition to this, I would like to add some different types of receptor downregulation, especially related to drug tolerance mechanism with examples of uses of cannabis and opiates.

http://bmcsystbiol.biomedcentral.com/articles/10.1186/1752-0509-1-48

http://www.jneurosci.org/content/jneuro/16/7/2172.full.pdf(nmda receptor)

http://www.sciencedirect.com/science/article/pii/0006899395011137

http://www.sciencedirect.com/science/article/pii/S0896627301800325

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728164/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728164/(nicotine receptors upregulation)

http://download.springer.com/static/pdf/418/bok%253A978-1-59745-197-0.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Fbook%2F10.1007%2F978-1-59745-197-0&token2=exp=1478483145~acl=%2Fstatic%2Fpdf%2F418%2Fbok%25253A978-1-59745-197-0.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Fbook%252F10.1007%252F978-1-59745-197-0*~hmac=01d3b2c7d648f6e6a6f2a2c5399a76b4741ad327deb6accd53b6fedfcab9cf6c (opioid)