46:-based phenomenon in which one receptor type, when bound to its ligand, becomes unable to further influence the signalling pathways by which it regulates cells and, in the case of cell surface membrane receptors, may thereafter be internalized. The desensitized receptor is degraded or freed of its activating ligand and re-cycled to a state where it is again able to respond to cognate ligands by activating its signalling pathways.
78:); cytokine and other non-G protein couple receptor types may also become heterologously desensitized by agents that activate protein kinase C but, perhaps more commonly, by agents that activate other protein kinases such as mitogen-activated protein kinase (
93:]. β-Blockade and direct inhibition of GRK2 restores β-adrenergic receptor signaling and has been proven beneficial for the treatment of chronic heart failure in humans and animal models. On the other hand, inactivating mutations of GRK1 lead to faulty
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Receptor desensitization, whether heterologous or homologous, may contribute to human pathology. For example, excessive desensitization due to the overexpression of GRK2 leads to the loss of β-adrenergic receptor signaling in hearts (see
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type, but in these cases desensitization is mediated by other types of receptor kinases. Homologous desensitization serves to limit or restrain a cell's responses to stimuli. However, some stimuli cause cells to activate
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that act to desensitize multiple types of receptors, thereby rendering a cell unresponsive to agonists of multiply receptor types. This commonly occurs with G protein coupled receptors (see
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53:, leaves a cell transiently unresponsive to agents that activate the desensitized receptor but not to agents that activate other receptors. It commonly occurs with
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Zeitz C, Robson AG, Audo I (2015). "Congenital stationary night blindness: an analysis and update of genotype-phenotype correlations and pathogenic mechanisms".
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that are mobilized during the receptor's activation. Homologous desensitization also occurs with cytokine and other types of receptors, such as those of the
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in GRK4γ or that cause an increase in G protein-coupled receptor kinase (GRK) activity cause serine phosphorylation and uncoupling of the
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Heterologous desensitization may occur in cells that are grossly overstimulated for prolonged times by a certain agents.
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Métayé T, Gibelin H, Perdrisot R, Kraimps JL (2005). "Pathophysiological roles of G-protein-coupled receptor kinases".
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Yamamoto H, Higa-Nakamine S, Noguchi N, Maeda N, Kondo Y, Toku S, Kukita I, Sugahara K (2014).
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143:"Regulatory effects of GRK2 on GPCRs and non-GPCRs and possible use as a drug target (Review)"
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187:"Desensitization by different strategies of epidermal growth factor receptor and ErbB4"
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121:, and excretion of sodium and water; it is associated with genetically based
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from its G protein effector GRK4. This impairs the kidney's
30:(also known as cross-desensitization) is the term for the
228:"Agonist-selective mechanisms of GPCR desensitization"
38:to which they are normally responsive. Typically,
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8:
147:International Journal of Molecular Medicine
97:receptor desensitization and are linked to
141:Han CC, Ma Y, Li Y, Wang Y, Wei W (2016).
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226:Kelly E, Bailey CP, Henderson G (2008).
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384:Symptoms and signs of mental disorders
49:This type of desensitization, termed
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337:Progress in Retinal and Eye Research
191:Journal of Pharmacological Sciences
59:G protein-coupled receptor kinases
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349:10.1016/j.preteyeres.2014.09.001
67:epidermal growth factor receptor
232:British Journal of Pharmacology
107:single nucleotide polymorphisms
91:Adrenergic receptor#β receptors
272:"heterologous desensitization"
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314:10.1016/j.cellsig.2005.01.002
125:in humans and animal models.
101:, a non-progressive form of
57:where it is mediated by the
28:Heterologous desensitization
18:Heterologous desensitization
55:G protein-coupled receptors
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51:homologous desensitization
115:renal sodium reabsorption
234:. 153 Suppl 1: S379–88.
34:of cells to one or more
240:10.1038/sj.bjp.0707604
160:10.3892/ijmm.2016.2720
123:essential hypertension
204:10.1254/jphs.13r11cp
302:Cellular Signalling
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129:References
61:(GRK) and
95:rhodopsin
378:Category
365:45696921
357:25307992
322:15894165
258:18059321
213:24553453
169:27573285
119:diuresis
63:arestins
44:receptor
36:agonists
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361:S2CID
42:is a
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