Breaking News
November 14, 2018 - Health Tip: Limit Fat, Sugar and Salt in Your Child’s Diet
November 14, 2018 - CA 19-9 Blood Test (Pancreatic Cancer): MedlinePlus Lab Test Information
November 14, 2018 - Old drug could have new use helping sick premature babies
November 14, 2018 - Surgery, not antibiotics, should remain first-line treatment for appendicitis | News Center
November 14, 2018 - Researchers to develop sports-specific classification system for blind football
November 14, 2018 - Preschool children show awake responses to naptime nonsense words
November 14, 2018 - Survey shows negative effect of vulvovaginal atrophy symptoms on quality of life for women
November 14, 2018 - Study sheds light on mechanisms that prevent autoimmune attack
November 14, 2018 - Sleep quality found to be worse for women who undergo surgical menopause
November 14, 2018 - New study provides deeper insight into chromosome segregation during mitosis
November 14, 2018 - Inhibition of one protein clears toxic clumps seen in Parkinson’s disease, study finds
November 14, 2018 - Appendix removal is linked to lower risk of Parkinson’s
November 14, 2018 - Lifting weights for less than an hour a week may reduce cardiovascular disease risk
November 14, 2018 - Pulmonary rehabilitation rarely received by hospitalized COPD patients despite health benefits
November 14, 2018 - New anti-HER2 drug shows promising anti-tumor activity in gullet, stomach and bowel cancers
November 14, 2018 - Regular head circumference assessment of preterm babies can help identify long-term IQ problems
November 14, 2018 - Brigham investigators examine opioid use among Massachusetts adolescents, prescription trends
November 14, 2018 - Study defines biomarker in response to treatment of castration-resistant prostate cancer
November 14, 2018 - Study identifies potential therapeutic strategy for patients with clear cell renal cancer
November 14, 2018 - Bausch Health Announces U.S. Launch of Bryhali (halobetasol propionate) Lotion, 0.01%, for Plaque Psoriasis In Adults
November 14, 2018 - Alpha Fetoprotein (AFP) Tumor Marker Test: MedlinePlus Lab Test Information
November 14, 2018 - Researchers evaluate controversial treatment for Parkinson’s disease psychosis
November 14, 2018 - AI could help veterinarians code their notes
November 14, 2018 - Pre-schoolers with autism thrive in mainstream classroom settings
November 14, 2018 - Individual and work-related factors may help promote hospital physician engagement, finds study
November 14, 2018 - Complementary and alternative medicine is widely used by general population in England
November 14, 2018 - Study reveals link between tobacco availability and smoking during pregnancy
November 14, 2018 - Purdue researchers develop translucent base for silicon patches to deliver exact doses of biomolecules
November 14, 2018 - New technology based on moths and magnets could help treat genetic diseases
November 14, 2018 - Concussion-Related Biomarkers Vary Based on Sex, Race
November 14, 2018 - One more year of high school may shape waistlines later in life
November 14, 2018 - Dissecting high drug costs – Scope
November 14, 2018 - Study shows novel strategy to reduce breast cancer bone metastasis
November 14, 2018 - Empowering the NHS through Industry Partnerships
November 14, 2018 - One size does not fit all in obesity treatment, study finds
November 14, 2018 - Seeking ways to prevent ‘secondary cataracts’
November 14, 2018 - Change Within the Eye May Be Early Warning for Macular Degeneration
November 14, 2018 - Study of 500,000 people clarifies the risks of obesity
November 14, 2018 - Ultrasound releases drug to alter activity in targeted brain areas in rats | News Center
November 14, 2018 - Umass Amherst researchers battle against youth suicide in rural Alaska Native communities
November 14, 2018 - Cancer stem cells depend on amino acid metabolism, and it’s proving to be their Achilles’ heel
November 14, 2018 - Epigenetic link found between prenatal exposure to maternal smoking and offspring’s cardio-metabolic health
November 14, 2018 - Meditation, music may change biomarkers of cellular aging and Alzheimer’s disease in older adults
November 14, 2018 - Multidisciplinaryresearch teams selected to study age-related brain disorders
November 14, 2018 - The Current issue of “The view from here” is concerned with Informatics
November 14, 2018 - Researchers identify tool to help transgender women have a more authentic voice
November 14, 2018 - Four faculty members appointed to endowed professorships | News Center
November 13, 2018 - Research finds strongest evidence yet that obesity causes depression
November 13, 2018 - Researchers compare stools of breastfed and formula-fed infants
November 13, 2018 - Entasis Therapeutics Announces Zoliflodacin Phase 2 Results Published in The New England Journal of Medicine
November 13, 2018 - Gene changes driving myopia reveal new focus for drug development
November 13, 2018 - $6 million grant to support study of preeclampsia, atherosclerosis links | News Center
November 13, 2018 - Beneficial gut microbes metabolize high-fiber diet to improve heart health in mouse model
November 13, 2018 - Excessive use of social media through visual postings linked to increase in narcissistic traits
November 13, 2018 - Study finds why obesity both fuels cancer growth and helps immunotherapy to kill tumors
November 13, 2018 - Women prefer and invest more in daughters, while men favor sons
November 13, 2018 - With hospitalization losing favor, judges order outpatient mental health treatment
November 13, 2018 - Transgenic rat model may provide new insights into cerebral amyloid angiopathy
November 13, 2018 - Study identifies factors tied to greater risk of advanced liver disease in cystic fibrosis patients
November 13, 2018 - Risk of blindness among premature babies with low levels of blood platelets
November 13, 2018 - A new strategy for combatting antibiotic-resistant infections
November 13, 2018 - Study aims to find which outreach method is more effective at improving cancer screening rates
November 13, 2018 - Insufficient sleep duration linked with unhealthy lifestyle profile among children
November 13, 2018 - IIASA researchers introduce new, simple measure for human wellbeing
November 13, 2018 - Magnetic nanosprings used as targeted drug delivery agents for anticancer therapy
November 13, 2018 - Scientists examine FCMs containing silver nanoparticles
November 13, 2018 - Failed DNA repair triggers chromosomal chaos
November 13, 2018 - Study shows new emerging role of osteopontin in HCV-related hepatocellular carcinoma
November 13, 2018 - Food insecurity during pregnancy linked to severity of neonatal abstinence syndrome
November 13, 2018 - Majority of Americans are concerned about health threat posed by antibiotic resistance
November 13, 2018 - Addition of Elotuzumab Ups PFS in Refractory Multiple Myeloma
November 13, 2018 - Study finds women with pregnancy-related nausea, vomiting use marijuana more
November 13, 2018 - Lethal heart rhythm more likely to be found in patients with common heart failure
November 13, 2018 - Study provides new clues to origin and development of multiple sclerosis
November 13, 2018 - Climate change could pose threat to male fertility
November 13, 2018 - Researchers discover how mitochondria deploy a powerful punch against disease-causing bacteria
November 13, 2018 - AHA: Traumatic Childhood Could Increase Heart Disease Risk in Adulthood
November 13, 2018 - Feeling the Burn? | NIH News in Health
November 13, 2018 - Women’s birth canals in Kenya, Korea, Kansas not the same: study
November 13, 2018 - Fecal microbiota transplantation effective against ICI-associated colitis
Study upends conventional view of opioid mechanism of action

Study upends conventional view of opioid mechanism of action

image_pdfDownload PDFimage_print

News Release

Thursday, May 10, 2018

NIH-funded scientists find new molecular target for developing safer pain medications.

A new discovery shows that opioids used to treat pain, such as morphine and oxycodone, produce their effects by binding to receptors inside neurons, contrary to conventional wisdom that they acted only on the same surface receptors as endogenous opioids, which are produced naturally in the brain. However, when researchers funded by the National Institute on Drug Abuse (NIDA) used a novel molecular probe to test that common assumption, they discovered that medically used opioids also bind to receptors that are not a target for the naturally occurring opioids. NIDA is part of the National Institutes of Health.

This difference between how medically used and naturally made opioids interact with nerve cells may help guide the design of pain relievers that do not produce addiction or other adverse effects produced by morphine and other opioid medicines.

“This ground-breaking study has uncovered important distinctions between the opioids that our brain makes naturally and therapeutic opioids that can be misused,” said NIDA Director Nora D. Volkow, M.D. “This information can be mined to better understand the potential adverse actions of medically prescribed opioids and how to manipulate the endogenous system to achieve optimal therapeutic results without the unhealthy side effects of tolerance, dependence, or addiction.”

Naturally occurring opioids and medically used opioids alike bind to the mu-opioid receptor, a member of a widespread family of proteins known as G protein-coupled receptors (GPCRs). Recent advances in understanding the three-dimensional structure of GPCRs have enabled researchers to create a new type of antibody biosensor, called a nanobody, that generates a fluorescent signal when a GPCR is activated. This enables scientists to track chemicals as they move through cells and respond to stimuli.

Using this nanobody, the researchers first showed that when a naturally occurring opioid binds to and activates the mu-receptor on the surface of a neuron, receptor molecules enter the cell inside what is known as an endosome. There, the mu-receptor remains activated over a period of several minutes, which itself was a new discovery, since it was believed that the opioid receptor is only activated on the surface of nerve cells. Proteins that interact with receptors on the cell surface control all sorts of biological processes and provide targets for therapeutic intervention.

With opioid medications, however, the researchers made two additional discoveries.  First, there are large differences across a range of clinically relevant opioid drugs in how strongly they induce receptor activation in endosomes. Second, the opioid drugs uniquely induce rapid nanobody signaling, within tens of seconds, in an internal cellular structure known as the Golgi apparatus in the main body of the neuron. Further investigation showed that therapeutic opioids also uniquely activate mu-opioid receptors in related structures, known as Golgi outposts, in the long, branched structures of neurons.

Based on these findings, the researchers hypothesize that current medically used opioids distort the normal time and spatial sequence of mu-opioid receptor activation and signaling. This distortion may provide the mechanistic link that explains the undesired side effects of opioid medicines suggests new avenues for designing agents that do not produce addiction or other adverse effects associated with these drugs.

“This new biosensor opens our eyes to a previously unknown level of diversity and specificity in the cellular actions of opioids,” said Dr. Miriam Stoeber, the study’s first author. Dr. Mark von Zastrow, senior author of the study, added, “We were surprised to see that drugs such as morphine activate opioid receptors in a location at which naturally occurring opioids do not.”

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

About the National Institute on Drug Abuse (NIDA): The National Institute on Drug Abuse (NIDA) is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world’s research on the health aspects of drug use and addiction. The Institute carries out a large variety of programs to inform policy, improve practice, and advance addiction science. Fact sheets on the health effects of drugs and information on NIDA research and other activities can be found at www.drugabuse.gov, which is now compatible with your smartphone, iPad or tablet. To order publications in English or Spanish, call NIDA’s DrugPubs research dissemination center at 1-877-NIDA-NIH or 240-645-0228 (TDD) or email requests to drugpubs@nida.nih.gov. Online ordering is available at drugpubs.drugabuse.gov. NIDA’s media guide can be found at www.drugabuse.gov/publications/media-guide/dear-journalist, and its easy-to-read website can be found at www.easyread.drugabuse.gov. You can follow NIDA on Twitter and Facebook.

About the National Institutes of Health (NIH):
NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

Article

Stoeber, et al. A genetically encoded biosensor reveals location bias of opioid drug action. May 10, 2018, Neuron. DOI: 10.1016/j.neuron.2018.04.021

###

Tagged with:

About author

Related Articles