Mu-opioid receptors (MORs) exhibit rapid desensitization and internalization during exposure to various opioid agonists. In some studies, however, morphine has been observed to produce little MOR desensitization or internalization. We examined desensitization in mature rat locus ceruleus (LC) neurons and confirmed that morphine is a very poor desensitizing agent, whereas [D-Ala2,N-MePhe4,Gly-ol...

There is ongoing debate about the role of G protein-coupled receptor kinases (GRKs) in agonist-induced desensitization of the μ-opioid receptor (MOPr) in brain neurons. In the present paper, we have used a novel membrane-permeable, small-molecule inhibitor of GRK2 and GRK3, Takeda compound 101 (Cmpd101; 3-[[[4-methyl-5-(4-pyridyl)-4H-1,2,4-triazole-3-yl] methyl] amino]-N-[2-(trifuoromethyl) ben...

Whole-cell or outside-out patch recordings were used to investigate the effects of protons and positive modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on the desensitization of glutamate-evoked AMPA receptor currents in isolated hippocampal CA1 neurons. Protons inhibited glutamate-evoked currents (IC(50) of 6.2 pH units) but also enhanced the apparent ra...

Morphine has been widely accepted as the opioid agonist that sustains signaling because it does not cause receptor desensitization or internalization. This notion has led to the hypothesis that long-term morphine treatment initiates downstream adaptations that underlie tolerance and dependence. This study uses whole-cell recordings from neurons in the locus ceruleus to measure the potassium cur...

There is ongoing debate about the role of G protein–coupled receptor kinases (GRKs) in agonist-induced desensitization of the m-opioid receptor (MOPr) in brain neurons. In the present paper, we have used a novel membrane-permeable, small-molecule inhibitor of GRK2 and GRK3, Takeda compound 101 (Cmpd101; 3-[[[4-methyl-5-(4-pyridyl)-4H-1,2,4-triazole-3-yl] methyl] amino]N-[2-(trifuoromethyl) benz...

OBJECTIVE To discuss the pathophysiology of vancomycin-induced immediate hypersensitivity reactions, review the process of vancomycin desensitization, and provide specific directions for ordering and preparing rapid and slow desensitization protocols. DATA SOURCES A MEDLINE search (1966-February 2001) of English-language literature pertaining to vancomycin desensitization and hypersensitivity...

Components of Meichenbaum's cognitive-behavior modification treatment for test anxiety were varied in a 2 × 2 factorial design. Desensitization and cognitive treatments were either given or not given. The resultant conditions were (a) desensitization only, (b) cognitive only, (c) the combination cognitive plus desensitization,, and (d) neither cognitive nor desensitization (control). Each test-...

BACKGROUND AND PURPOSE Antiepileptic drug (AED)-associated cutaneous adverse drug reactions can lead to the discontinuation of medications. The aim of this study was to determine the long-term efficacy and safety of performing desensitization to oxcarbazepine. METHODS This study involved 20 patients who exhibited cutaneous adverse drug reactions associated with oxcarbazepine use between July ...

In whole-cell recordings from mammalian CNS neurons, AMPA-preferring glutamate receptors exhibit strong desensitization in response to AMPA, glutamate, and quisqualate, but not to kainate or domoate. Such desensitization is reduced by lectins, by the nootropic drug aniracetam, and by diazoxide. None of these compounds strongly modulate responses to kainate and domoate, consistent with the appar...

The transient receptor potential channel subtypes V1 (TRPV1) and A1 (TRPA1) play a critical role in the development of hyperalgesia in inflammatory pain models. Although several studies in animals and humans have demonstrated that capsaicin (CAP), a TRPV1-specific agonist, and mustard oil (MO), a TRPA1 agonist, evoke responses that undergo functional cross-desensitization in various models, the...