In the immune system, signaling by G protein-coupled receptors (GPCRs) is crucial for the activity of multiple mediators, including chemokines, leukotrienes, and neurotransmitters. GPCR kinases (GRKs) and arrestins control GPCR signaling by mediating desensitization and thus, regulating further signal propagation through G proteins. Recent evidence suggests that the GRK-arrestin desensitization...

Strategies for inducing immune tolerance are fundamentally similar across a spectrum of immune-mediated disorders, including allergic disease, autoimmunity, and rejection of allografts. In each case, the objective of establishing an immunoregulatory balance is challenged by variable upswings in effector cell populations and proinflammatory mediators of immunity, requiring careful, and innovativ...

The study was carried out to desensitize spontaneously active isolated chick rectum with salbutamol in log doses starting from 100 nanogram and resensitize with various drugs as a result to revive the desensitized tissue and respond to Salbutamol. The tissue response after desensitization to alpha, beta adrenergic and muscarinic acetylcholine receptor antagonists was isotonically recorded for 1...

Usage of cancer chemotherapeutics drugs can be associated with adverse drug reactions. When IgE-mediated drug reactions are formed following administration of a chemotherapeutic drug that is a drug of choice, drug desensitization protocols can be helpful. Hypersensitivity reactions can be allergic or nonallergic, but the clinical manifestations are similar. Rapid drug desensitization (RDD) is e...

Tolerance and dependence result from long-term exposure to opioids, and there is growing evidence linking acute receptor desensitization to these more long-term processes. Receptor desensitization encompasses a series of events leading to the loss of receptor function and internalization. This study examines the onset and recovery from desensitization in locus ceruleus neurons recorded in brain...

When subjected to prolonged exposure to nicotinic agonists, nicotinic acetylcholine receptors undergo desensitization, resulting in an inactive receptor that does not allow for the passage of ions. The induction of desensitization of diverse nicotinic acetylcholine receptor subtypes in muscle, ganglia, or brain is likely to play important modulatory roles in synaptic transmission. Furthermore, ...

Desensitization of heterologously expressed metabotropic glutamate receptor 5a (mGluR5a) was examined in rat sympathetic neurons. Calcium currents in cells expressing mGluR5a exhibited substantial inhibition in response to glutamate exposure. In the continued presence of glutamate, inhibition attenuated rapidly over the course of about a minute. Desensitization was eliminated when a nonhydrolyz...

Desensitization of crayfish glutamate channels was studied in outside-out patches employing an improved fast drug-application technique. Low concentrations of glutamate produced substantial desensitization without correlation with the detected number of open channels. The desensitization time constant (tau(D)) was found to be independent of glutamate concentration (0.3-20 mM). These results sug...

For decades we have understood that G-protein-coupled receptors (GPCRs) are crucial links in the relay of information from extracellular stimuli to intracellular responses. Their importance is highlighted by the wide variety of GPCRs encoded in the human genome (Fredriksson et al., 2003; Perez, 2003) and the multiple mechanisms by which they are regulated (Clark, 1986; Palczewski and Benovic, 1...

Activation of P2X2 receptor channels (P2X2Rs) is characterized by a rapid current growth accompanied by a decay of current during sustained ATP application, a phenomenon known as receptor desensitization. Using rat, mouse, and human receptors, we show here that two processes contribute to receptor desensitization: bath calcium-independent desensitization and calcium-dependent desensitization. C...