Homologous desensitization
Encyclopedia
Homologous desensitization occurs when a receptor
decreases its response to a signalling molecule when that agonist
is in high concentration. It is a process whereby after prolonged agonist exposure, the receptor is uncoupled from its signaling cascade, and thus the biological effect of receptor activation is attenuated.
Homologous desensitization should not be confused with heterologous desensitisation
, which is a different process whereby repeated stimulation of a receptor by one agonist results in desensitivity to a range of other agonists.
as an example):
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
decreases its response to a signalling molecule when that agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
is in high concentration. It is a process whereby after prolonged agonist exposure, the receptor is uncoupled from its signaling cascade, and thus the biological effect of receptor activation is attenuated.
Homologous desensitization should not be confused with heterologous desensitisation
Heterologous desensitisation
Heterologous desensitisation is the broad unresponsiveness to a variety of other agonists, after prolonged stimulation by one agonist....
, which is a different process whereby repeated stimulation of a receptor by one agonist results in desensitivity to a range of other agonists.
Mechanism
The mechanism of homologous desensitization is as follows (using the β2 receptorBeta-2 adrenergic receptor
The beta-2 adrenergic receptor , also known as ADRB2, is a beta-adrenergic receptor, and also denotes the human gene encoding it.-Gene:The gene is intronless...
as an example):
- Agonist binds and activates receptor which changes to an active conformational state.
- Beta adrenergic receptor kinaseBeta adrenergic receptor kinaseBeta adrenergic receptor kinase is a serine/threonine intracellular kinase. It is activated by PKA and its target is the beta adrenergic receptor...
(BARK), a cytoplasmic kinaseKinaseIn chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
is activated and phosphorylatesPhosphorylationPhosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
the C-terminus of the β2 receptor. - Such phosphorylation increases the affinity of β-arrestinArrestinArrestins are a small family of proteins important for regulating signal transduction.-Function:Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of G protein-coupled receptors in the visual rhodopsin system by Hermann Kühn and co-workers and...
for the receptor, resulting in uncoupling of the α subunitGs alpha subunitThe Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:...
of the heterotrimeric G-protein from the receptor producing desensitization.