Heterologous desensitisation

Heterologous desensitisation (also known as cross-desensitisation) is the term for the unresponsiveness of cells to one or more agonists to which they are normally responsive. Typically, desensitization is a Receptor (biochemistry)-based phenomenon in which one receptor type, when bound to its ligand, becomes unable to further influence the signaling 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 signaling pathways. This form of desensitization, termed homologous desensitization, leaves cells transiently unresponsive to agents that activate the desensitized receptor but not to agents that activate other receptors; it commonly occurs with G protein coupled receptors as well as cytokine and other types of receptors like those of the epidermal growth factor receptor type.. Homologous desensitization serves to limit or restrain a cells responses to stimuli. However, some stimuli cause cells to active protein kinase Cs which in turn phosphorylate and thereby 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 Protein kinase C#Function); cytokine and other non-G protein couple receptor types may likewise become heterologously desensitized by agents which activate protein kinase C but also, and perhaps more commonly, by agents that activate other protein kinases such as mitogen-activated protein kinase (p38 MAP kinase). Heterologous desensitization may also occur in cells that are grossly over-stimulated for prolonged times by certain agents.