Prolonged exposure of most fast neurotransmitter-operated ion channels to agonist drives the receptors into a nonfunctional, or desensitized, state. Despite extensive investigation, desensitization remains a thoroughly characterized, yet poorly understood, process. Part of the difficulty in elucidating the mechanism of desensitization has been an inability to resolve the kinetics of both agonis...

Several neurochemical and electrophysiological studies have shown that neuronal nicotinic receptors are desensitized by pretreatment with lower agonist concentrations than are required to activate the receptors, but the extent of desensitization and agonist concentration required to produce desensitization vary depending upon receptor subtype. Recently, we reported that nicotinic agonists will ...

We investigated which of the major actions of local anesthetics (i.e., inhibition of phospholipase A2, interaction with Ca++ channels or blockade of receptor) was responsible for the inhibition of acetylcholine-induced desensitization in guinea pig ileal longitudinal muscle. Desensitization was inhibited by amine local anesthetics and related compounds in the order of potency quinacrine > chlor...

BACKGROUND Aspirin remains the mainstay of anti-platelet therapy in cardiac patients. However, if a patient is allergic to aspirin and dual anti-platelet therapy is indicated - such as with percutaneous coronary intervention (PCI), then there is no clear guidance. One possibility is aspirin desensitization. A variety of protocols exist for the rapid desensitization of patients with aspirin alle...

Background Recombinant human erythropoietin, such as epoetin alfa and darbepoetin alfa, is an important therapy for anemia due to chronic renal failure. Allergy to recombinant human erythropoietin and the need for desensitization are rare. Case presentation We report here a novel epoetin alfa outpatient desensitization protocol in a girl who developed delayed cutaneous hypersensitivity to sub...

Aspirin-exacerbated respiratory disease (AERD) is a chronic inflammatory disease characterized by chronic rhinosinusitis, nasal polyposis, asthma, and airway reactivity to aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs). For patients who have inadequately controlled rhinosinusitis and/or asthma despite treatment with topical corticosteroids and leukotriene-modifying drugs, aspiri...

Conditions have been developed for desensitizing the P-adrenergic receptor-coupled adenylate cyclase of turkey erythrocytes in a cell-free system. Desensitization is observed when cell lysates are incubated with isoproterenol or cAMP analogs for 30 min at 37 “C. Maximally effective concentrations of isoproterenol produce a 41.0 2 1.55% loss of iosproterenol-stimulated and a 15.0 2 2.35% loss o...

Although interleukin 1 (IL-1) receptor signaling events in T helper lymphocytes are incompletely characterized, events associated with translocation of the transcription factor NF-kappa B are receptor-proximal assays of ligand-initiated responses. In this report we demonstrate that the transient nature of IL-1-induced NF-kappa B nuclear translocation occurs as a consequence of ligand-induced re...

In rat locus coeruleus (LC) neurons, alpha 2 adrenoceptors, mu-opioid and somatostatin receptors all activate the same potassium conductance. Chronic treatment with morphine causes a loss of sensitivity that is specific to the mu-opioid response, with no change in the alpha 2 adrenoceptor-mediated response. Acute desensitization induced by opioid, somatostatin, and alpha 2-adrenoceptor agonists...

Prolonged or repeated activation of many G protein-coupled receptors induces rapid desensitization followed by a period during which receptors are resensitized. In this study, concanavalin A (Con A) and monensin were used to investigate the mechanisms of desensitization and resensitization of the neurokinin-1 receptor. Con A inhibits internalization, whereas monensin prevents receptor recycling...