tracking-drug-induced-changes-receptor-post-internalization

Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis

The intracellular trafficking of receptors is a collection of complex and highly controlled processes. Receptor trafficking modulates signaling and ...

university of california irvine

Queen's University

An ancient malady.

To evaluate the effects of epidural, spinal, and general anesthesia on pain after lower-limb amputation.

Effects of anesthesia on pain after lower-limb amputation.

HIV testing in the UK.

The mu and delta types of opioid receptors form heteromers that exhibit pharmacological and functional properties distinct from those of homomeric receptors. To characterize these complexes in the brain, we generated antibodies that selectively recognize the mu-delta heteromer and blocked its in vitro signaling. With these antibodies, we showed that chronic, but not acute, morphine treatment caused an increase in the abundance of mu-delta heteromers in key areas of the central nervous system that are implicated in pain processing. Because of its distinct signaling properties, the mu-delta heteromer could be a therapeutic target in the treatment of chronic pain and addiction.

Increased abundance of opioid receptor heteromers after chronic morphine administration.

The late diagnosis of HIV in patients across the UK is an increasing problem. Here, we report on a retrospective case-notes audit carried out to assess the impact of the 2008 UK HIV testing guidelines on clinical practice and identify missed opportunities for HIV testing. The audit was carried out in 2010 and focussed on patients with newly diagnosed HIV at centres providing adult HIV services across the UK. Data were collected on 1,112 patients, of whom 52.2% were found to have a late HIV diagnosis as defined as a CD4 T lymphocyte count of <350 cells/mm3. Most patients (62.6%) were diagnosed in traditional settings, with a significant increase in those diagnosed with HIV in non-traditional settings (33%) compared with the 2003 audit (18.5%) (p<0.001). The most frequent indicator conditions that patients had experienced were chronic diarrhoea or weight loss, sexually transmitted infection, blood dyscrasia or lymphadenopathy. A quarter of patients were identified as having had a missed opportunity for earlier diagnosis. Based on our results, we suggest that HIV testing needs to continue to expand across clinical settings to reduce the number of patients living with undiagnosed HIV infection.

HIV diagnoses and missed opportunities. Results of the British HIV Association (BHIVA) National Audit 2010.

Migrant patients' access to HIV care: testing should always be free.

Opioid receptors are the sites of action for morphine and the other opioid drugs. Abundant evidence now demonstrates that different opioid receptor types can physically associate to form heteromers. Understandings of the nature, behavior, and role of these opioid receptor heteromers are developing. Owing to their constituent monomers' involvement in analgesia, mu/delta opioid receptor (M/DOR) heteromers have been a particular focus of attention. There is now considerable evidence demonstrating M/DOR to be an extant and physiologically relevant receptor species. Participating in the cellular environment as a distinct receptor type, M/DOR availability is complexly regulated and M/DOR exhibits unique pharmacology from that of other opioid receptors (ORs), including its constituents. M/DOR appears to have a range of actions that vary in a ligand- (or ligands-) dependent manner. These actions can meaningfully affect the clinical effects of opioid drugs: strategies targeting M/DOR may be therapeutically useful. This review presents and discusses developments in these understandings with a focus on the molecular nature and activity of M/DOR in the context of therapeutic potentials.

Molecular Perspectives for mu/delta Opioid Receptor Heteromers as Distinct, Functional Receptors.

Futility of CD4+ monitoring in HIV-1 patients with CD4+ cell count above 350 cells/μl on suppressive antiretroviral therapy.

The kappa opioid receptor (KOR) and the endogenous peptide-ligand dynorphin have received significant attention due the involvement in mediating a variety of behavioral and neurophysiological responses, including opposing the rewarding properties of drugs of abuse including opioids. Accumulating evidence indicates this system is involved in regulating states of motivation and emotion. Acute activation of the KOR produces an increase in motivational behavior to escape a threat, however, KOR activation associated with chronic stress leads to the expression of symptoms indicative of mood disorders. It is well accepted that KOR can produce analgesia and is engaged in chronic pain states including neuropathic pain. Spinal studies have revealed KOR-induced analgesia in reversing pain hypersensitivities associated with peripheral nerve injury. While systemic administration of KOR agonists attenuates nociceptive sensory transmission, this effect appears to be a stress-induced effect as anxiolytic agents, including delta opioid receptor agonists, mitigate KOR agonist-induced analgesia. Additionally, while the role of KOR and dynorphin in driving the dysphoric and aversive components of stress and drug withdrawal has been well characterized, how this system mediates the negative emotional states associated with chronic pain is relatively unexplored. This review provides evidence that dynorphin and the KOR system contribute to the negative affective component of pain and that this receptor system likely contributes to the high comorbidity of mood disorders associated with chronic neuropathic pain.

Article	Year
An ancient malady. The American journal of medicine\| PubMed ID: 17145246	2006
Effects of anesthesia on pain after lower-limb amputation. Journal of clinical anesthesia\| PubMed ID: 17175430	2006
HIV testing in the UK. Lancet (London, England)\| PubMed ID: 19647601	2009
Increased abundance of opioid receptor heteromers after chronic morphine administration. Science signaling\| PubMed ID: 20647592	2010
HIV diagnoses and missed opportunities. Results of the British HIV Association (BHIVA) National Audit 2010. Clinical medicine (London, England)\| PubMed ID: 23101142	2012
Migrant patients' access to HIV care: testing should always be free. BMJ (Clinical research ed.)\| PubMed ID: 24285168	2013
Molecular Perspectives for mu/delta Opioid Receptor Heteromers as Distinct, Functional Receptors. Cells\| PubMed ID: 24709907	2014
Futility of CD4+ monitoring in HIV-1 patients with CD4+ cell count above 350 cells/μl on suppressive antiretroviral therapy. AIDS (London, England)\| PubMed ID: 25418545	2014
Does the kappa opioid receptor system contribute to pain aversion? Frontiers in pharmacology\| PubMed ID: 25452729	2014

Edmund Ong

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