How are GPCRs desensitized?

GPCRs can be desensitized following activation by agonists by becoming phosphorylated by members of the family of G protein-coupled receptor kinases (GRKs). Phosphorylated receptors are then bound by arrestins, which prevent further stimulation of G proteins and downstream signaling pathways.

What does nociceptive GPCR respond to?

Noxious stimuli are “actually or potentially tissue damaging events” that need to act on nociceptors in order to cause pain. Accordingly, nociceptors are viewed as “sensory receptors that are capable of transducing and encoding noxious stimuli”.

What causes receptor desensitization?

Thus, heterologous desensitization may be caused by any cellular signaling that leads to activation of second-messenger-activated protein kinases that then phosphorylate sites on a particular receptor. The association of arrestin with the receptor interferes with G-protein coupling and promotes internalization.

What are the effects of GPCR desensitization in humans?

1. Desensitization: a protective measure to block overstimulation G protein-coupled receptors (GPCRs) transduce signals originating from the extracellular space to the biochemical and genetic machinery inside a cell and lead to responses including vision, olfaction, taste, vascular tone, muscle contraction, pain and behavior.

What does tachyphylaxis mean in terms of GPCR?

The term tachyphylaxis refers to the decreased responsiveness of a cell to repeated stimulation with drug, and can be due to both processes of GPCR-transducer uncoupling (acute or short-term desensitization) and GPCR downregulation (long-term desensitization) ( Fig. 1 ).

Which is a consequence of overstimulation of GPCR?

While GPCR signaling is essential, overstimulation can be deleterious, resulting in cellular toxicity or uncontrolled cellular growth. Accordingly, nature has developed a number of mechanisms for limiting GPCR signaling, which are broadly referred to as desensitization, and refer to a decrease in response to repeated or continuous stimulation.

What are the effects of overstimulation of G protein coupled receptors?

G protein-coupled receptors (GPCRs) transduce a wide array of extracellular signals and regulate virtually every aspect of physiology. While GPCR signaling is essential, overstimulation can be deleterious, resulting in cellular toxicity or uncontrolled cellular growth.