A5079132033- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Pain Mechanisms and Treatments
- Pharmacological Receptor Mechanisms and Effects
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Health Systems, Economic Evaluations, Quality of Life
- Musculoskeletal pain and rehabilitation
- Stress Responses and Cortisol
- Opioid Use Disorder Treatment
- Pain Management and Placebo Effect
- Chemical Synthesis and Analysis
- Attention Deficit Hyperactivity Disorder
- Neuroendocrine regulation and behavior
- Healthcare Policy and Management
- Memory and Neural Mechanisms
- Hypothalamic control of reproductive hormones
- Peptidase Inhibition and Analysis
- Pelvic floor disorders treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Urinary Bladder and Prostate Research
- Urinary Tract Infections Management
- Pharmacological Effects and Assays
- Mobile Health and mHealth Applications
- Cancer, Stress, Anesthesia, and Immune Response
University of California, Los Angeles
2014-2023
Healthpoint
2016-2023
Health Outcomes Solutions (United States)
2014-2022
National Institutes of Health
2020
Center for Neuro-Oncology
2006-2020
Zero to Three
2020
Neurobehavioral Systems
1991-2019
Westwood College
2019
Foundation for Physical Medicine and Rehabilitation
2016
Georgetown University
2016
Opiate drugs have potent analgesic and addictive properties. These interact with receptors that also mediate the response to endogenous opioid peptide ligands. However, for opioids eluded definitive molecular characterization. By transient expression in COS cells screening an iodinated analog of enkephalin, a complementary DNA clone encoding functional δ receptor has been identified. The sequence shows homology G protein-coupled receptors, particular somatostatin, angiotensin, interleukin-8.
We have examined the endocytic trafficking of epitope-tagged δ and µ opioid receptors expressed in human embryonic kidney (HEK) 293 cells. These are activated by peptide agonists (enkephalins) as well alkaloid agonist drugs etorphine morphine. Enkephalins cause to internalize rapidly (t1/2 ~ 6 min) a mechanism similar that utilized number other classes receptor, indicated localization internalized transferrin-containing endosomes inhibition receptor internalization hypertonic media....
Chronic migraine is a disabling condition that affects hundreds of millions individuals worldwide. The development novel treatments has been slow, in part as result lack predicative animal models. We have developed new model chronic involving the use nitroglycerin (NTG), known trigger humans. intermittent administration NTG to mice resulted acute mechanical hyperalgesia with each exposure well progressive and sustained basal hyperalgesia. This occurred dose-dependent fashion persisted for...
μ-Opioid receptors are the pharmacological targets of endogenous opioid peptides and morphine-like alkaloid drugs. Previous studies transfected cells peripheral neurons indicate that rapidly internalized after activation by agonist etorphine but not morphine. To determine whether in central nervous system regulated a similar process agonist-selective internalization, μ-opioid were examined rat brain treatment animals with Internalized μ observed within 30 min intraperitoneal injection...
Buprenorphine is a mixed opioid receptor agonist-antagonist used clinically for maintenance therapy in opiate addicts and pain management. Dose-response curves buprenorphine-induced antinociception display ceiling effects or are bell shaped, which have been attributed to the partial agonist activity of buprenorphine at receptors. Recently, has shown activate receptor-like (ORL-1) receptors, also known as OP4 Here we demonstrate that buprenorphine, but not morphine, activates...
The primary structure of the opioid receptors have revealed that many structural features are conserved in other G protein-coupled also receptors. Upon exposure to agonists, some internalize rapidly, whereas structurally homologous do not. It is not known whether regulated by rapid endocytosis. In transfected Chinese hamster ovary cells expressing epitope-tagged wild type δ receptor, 100 nM [D-Ala2,D-Leu5]enkephalin causes internalization receptor within 30 min as determined confocal...
Chronic pain attenuates midbrain dopamine (DA) transmission, as evidenced by a decrease in opioid-evoked DA release the ventral striatum, suggesting that occurrence of chronic impairs reward-related behaviors. However, mechanisms which modifies transmission remain elusive. Using vivo microdialysis and microinjection drugs into mesolimbic system, we demonstrate mice rats microglial activation VTA compromises not only DA, but also other DA-stimulating drugs, such cocaine. Our data show loss...
Immunohistofluorescence studies of the rat central nervous system with antibodies to Phe-Met-Arg-Phe-NH 2 (molluskan cardioexcitatory peptide) revealed a widespread neuronal in brain, spinal cord, and posterior pituitary. Immunoreactive axons cell bodies were mainly located cortical, limbic, hypothalamic areas. Immunostaining serial sections brain pituitary showed that Phe-Met-Arg-Phe-NH2 immunoreactive neurons different from labeled by either Met-enkephalin or putative precursor...
δ-Opioid receptors are G-protein-coupled that regulate nociceptive and emotional responses. It has been well established distinct agonists acting at the same receptor can engage different signaling or regulatory This concept, known as biased agonism, important biological therapeutic implications. Ligand-biased responses described in cellular models, however, demonstrating physiological relevance of agonism vivo remains a major challenge. The aim this study was to investigate long-term...
<ns4:p>Opioid drugs are potent modulators of many physiological and psychological processes. When given acutely, they can elicit the signature responses euphoria analgesia that societies have coveted for centuries. Repeated, or chronic, use opioids induces adaptive allostatic changes modify neuronal circuitry create an altered normality — “drug-dependent” state. This state, at least exhibited by those maintained continuously on long-acting opioid such as methadone buprenorphine, is generally...
Opioid dependence is accompanied by neuroplastic changes in reward circuitry leading to a negative affective state contributing addictive behaviors and risk of relapse. The current study presents neuroimmune mechanism through which chronic opioids disrupt the ventral tegmental area (VTA) dopaminergic that contributes impaired behavior. was induced rodents treatment with escalating doses morphine. Microglial activation observed VTA following spontaneous withdrawal from morphine treatment....
Pain is a multidimensional experience and negative affect, or how much the pain “bothersome”, significantly impacts sufferers' quality of life. It well established that κ opioid system contributes to depressive dysphoric states, but whether this affect precipitated by occurrence chronic remains tenuous. Using model persistent pain, we show quantitative real-time-PCR, florescence in situ hybridization, Western blotting GTPgS autoradiography an upregulation expression function receptors (KORs)...