Desensitization

1.Drug desensitization refers to two related concepts. First, desensitization may be equivalent to drug tolerance and refers to subjects' reactions (positive or negative) to a drug reducing following its repeated use. 

2.desensitization, which refers to a biochemical effect where individual receptors become less responsive after repeated application of an agonist. This may be mediated by phosphorylation, for instance by beta adrenoceptor kinase at the beta adrenoceptor.

3.Desensitization is a result of either of continued presence of agonist specific for that receptor (homologous) or of a result of either a class of agonists working toward a “common goal” (heterologous desensitization).

4.There are two known mechanisms for desensitization (see Figure 10.19). a)decrease in response brought about by the covalent modifications produced by receptor phosphorylation and is quite rapid (seconds to minutes).

b)physical removal of receptors from the plasma membrane through a mechanism of receptor-mediated endocytosis and tends to require greater periods (minutes to hours). 

5.Its a very important process whereby cells can decrease their sensitivity to a particular neurotransmitter to prevent saturation of the system. 

Desensitization involves a complex series of events (Kobilka, 1992; Clark et al., 1999; Rosenbaum et al., 2009).

 For GPCRs, functional desensitization is defined as an increase in the concentration of neurotransmitter required to produce half-maximal stimulation of, for example, adenylyl cyclase. In practical terms, desensitization of receptor produces less response for a constant amount of transmitter.

6. How to treat desensitization ?

The procedure most commonly involves initially administering an extremely small amount of a medication (i.e., 1/10,000 of the usual dose). Then, over several hours, gradually increasing doses are given at regular intervals (such as every 15 minutes) until the full dose is reached.