PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Propofol discovery may aid development of new anesthetics

2013-09-23
(Press-News.org) Researchers at Washington University School of Medicine in St. Louis and Imperial College London have identified the site where the widely used anesthetic drug propofol binds to receptors in the brain to sedate patients during surgery.

Until now, it hasn't been clear how propofol connects with brain cells to induce anesthesia. The researchers believe the findings, reported online in the journal Nature Chemical Biology, eventually will lead to the development of more effective anesthetics with fewer side effects.

"For many years, the mechanisms by which anesthetics act have remained elusive," explained co-principal investigator Alex S. Evers, MD, the Henry E. Mallinckrodt Professor and head of the Department of Anesthesiology at Washington University. "We knew that intravenous anesthetics, like propofol, act on an important receptor on brain cells called the GABAA receptor, but we didn't really know exactly where they bound to that receptor."

Propofol is a short-acting anesthetic often used in patients having surgery. It wears off quickly and is less likely to cause nausea than many other anesthetics. But the drug isn't risk-free. Its potentially dangerous side effects include lowering blood pressure and interfering with breathing.

In an attempt to understand how propofol induces anesthesia during surgery, scientists have tried to identify its binding site within the gamma-aminobutyric acid type A (GABAA) receptor on brain cells. Activating these receptors — with propofol, for example — depresses a cell's activity.

Researchers have altered the amino acids that make up the GABAA receptor in attempts to find propofol's binding site, but Evers said those methods couldn't identify the precise site with certainty.

"In previous work to directly identify anesthetic binding sites, GABAA receptors had to be extracted from membranes and purified prior to performing the binding studies," he said. "Our method allowed us to study propofol binding to the intact receptor in its native membrane environment."

AUDIO: Researchers at Washington University School of Medicine in St. Louis and Imperial College in London have been studying propofol, the world's most widely used intravenous anesthetic. And the research team...
Click here for more information.

Having developed the techniques to analyze the interactions between anesthetics and GABAA receptors in their native environment, Evers' laboratory teamed up with a group at Imperial College that had been taking the same approach. Led by Nicholas P. Franks, PhD, professor of biophysics and anaesthetics, the group has spent years creating a photoanalogue of propofol that both behaves in precisely the same way as propofol and contains a labeling group that permanently attaches to its binding site on the GABAA receptor when exposed to a specific wavelength of light.

In creating the analogue of propofol, it's as if the researchers put a tiny hook onto the molecule so that when it binds to the GABAA receptor, it grabs onto the receptor and won't let go.

"Normally, an anesthetic drug binds to the GABAA receptor transiently," Franks explained. "But for the purposes of this research, we wanted to create an analogue that behaved exactly like propofol except that we could activate this chemical hook to permanently bind the drug to the receptor. The next step was then to extract the receptor, cut it into pieces and identify the precise piece of the protein where the propofol analogue had attached to the receptor. This was the tricky step that the Evers group at Washington University had perfected."

Evers and Franks believe this technique has implications beyond propofol and other anesthetics.

"Anesthetics have desirable effects — they induce anesthesia, for example — but they also have undesirable effects," Evers said. "Propofol can lower blood pressure or interfere with breathing, for example. By understanding precisely what the binding sites look like on the proteins that induce those potential problems, we eventually hope to design and select for drugs that have the benefits we want without dangerous side effects."

Using the techniques they have developed, Evers and Franks now plan to identify binding sites of other anesthetic agents. They believe their approach also can be used to study other types of drugs, such as psychiatric agents and anti-seizure drugs.



INFORMATION:



Funding for this research comes from the Medical Research Council, UK; the National Institute of General Medical Sciences (NIGMS) and the National Center for Research Resources of the National Institutes of Health (NIH); the Austrian Ministry of Science and Research and the European Seventh Framework Program.

NIH grant numbers PO1-GM47969, P41 RR00954 and UL1 RR024992.

Yip GMS, Chen ZW, Edge CJ, Smith EH, Dickinson R, Hohenester E, Townsend RR, Fuchs K, Sieghard W, Evers AS, Franks NP. A propofol binding site on mammalian GABAA receptors identified by photolabeling. Nature Chemical Biology, Advance Online Publication, Sept. 22, 2013. 10.1038/nchembio.1340

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.



ELSE PRESS RELEASES FROM THIS DATE:

Chronic aggressive behavior in boys: Epigenetic sources?

2013-09-23
Chronic aggressive behaviour exhibited by some boys from disadvantaged families may be due to epigenetic changes during pregnancy and early childhood. This is highlighted by two studies conducted by a team led by Richard E. Tremblay, professor emeritus at the University of Montreal and Moshe Szyf, professor at McGill University, published in the journal PLOS ONE. The first author of the two papers, Nadine Provençal, was jointly supervised by professors Szyf and Tremblay. Epigenetic changes possibly related to the prenatal environment In the first study, published in ...

Why do you want to eat the baby?

2013-09-23
What woman has not wanted to gobble up a baby placed in her arms, even if the baby is not hers? This reaction, which everyone has noticed or felt, could have biological underpinnings related to maternal functions. For the first time, an international team of researchers has found evidence of this phenomenon in the neural networks associated with reward. "The olfactory -- thus non-verbal and non-visual -- chemical signals for communication between mother and child are intense," explains Johannes Frasnelli, a postdoctoral researcher and lecturer at the University of Montreal's ...

Functional disability high among newly diagnosed older breast cancer patients

2013-09-23
Many older women with newly diagnosed breast cancer have difficulty accomplishing daily tasks, and African-Americans seem to be disproportionately affected. Those are the findings of a new study published early online in CANCER, a peer-reviewed journal of the American Cancer Society. The study's results suggest that many breast cancer patients could benefit from receiving therapy to improve their physical function. Many studies conducted in older adults have demonstrated that, compared with Caucasians, African-Americans are more likely to experience functional disability, ...

Breastfeeding fraught with early challenges for many first-time mothers

2013-09-23
Most new mothers in the United States begin breastfeeding when their children are born, but new research shows that those who report early concerns or problems with breastfeeding are nearly 10 times more likely to abandon breastfeeding within two months. In a new study 92 percent of new moms reported at least one breastfeeding concern three days after birth. The most predominant concern, in 52 percent of mothers, was infant feeding at the breast, which refers to the behavior of the baby, such as not "latching on" properly. Other common concerns included breastfeeding ...

Clinical trial strives to provide optimal care during high-risk pregnancies

2013-09-23
Researchers are conducting a clinical trial to help determine the best timing of delivery in preterm pregnancies complicated by poor fetal growth. Preliminary results from the trial, which are published early online in Ultrasound in Obstetrics & Gynecology, demonstrate better than expected health outcomes in this high-risk group of fetuses. Doctors are faced with a dilemma when deciding about the timing of delivery of a baby who does not grow adequately as a fetus, a condition called fetal growth restriction. To deliver early potentially exposes the baby to risks associated ...

Disaster relief donations track number of people killed, not number of survivors

2013-09-23
People pay more attention to the number of people killed in a natural disaster than to the number of survivors when deciding how much money to donate to disaster relief efforts, according to new research published in Psychological Science, a journal of the Association for Psychological Science. The donation bias can be reversed, however, with a simple change in terminology. "While fatalities have a severe impact on the afflicted community or country, disaster aid should be allocated to people affected by the disaster – those who are injured, homeless, or hungry," says ...

Research minimizes effects of federal produce standards on mushroom industry

2013-09-21
Strict requirements on the use of animal manures in fresh produce production imposed by the new federal food-safety law threatened to adversely impact the mushroom industry, which relies on horse and poultry manure for a specialized growth substrate. But a new study shows that heat generated during the traditional composting process -- originally developed to kill insect and fungal pests of mushrooms -- is adequate for eliminating human pathogens that might be present, according to researchers in Penn State's College of Agricultural Sciences. As a result of those findings, ...

NASA HS3 mission reveals Tropical Storm Humberto's hybrid core

2013-09-21
NASA's Global Hawk 872 flew over Tropical Storm Humberto on Sept. 16 and 17 after it was reborn from remnants of its earlier life cycle. Data from NASA 872 showed that the core had a hybrid structure. NASA's Global Hawk 872 unmanned aircraft took off at 10:42 a.m. EDT from NASA's Wallops Flight Facility, Wallops Island, Va., Sept. 16 to investigate newly reformed Tropical Storm Humberto. NASA 872 dispersed dropsondes throughout Humberto and gathered data on the environment of the storm. A sonde is a device that measures winds, temperature, and humidity. The instrument ...

UC Davis researchers find Neandertals, not modern humans, made first bone tools

2013-09-21
One day in 2011, undergraduate student Naomi Martisius was sorting through tiny bone remnants in the University of California, Davis, paleoanthropology lab when she stumbled across a peculiar piece. The bone fragment, from a French archaeological site, turned out to be a part of an early specialized bone tool used by a Neandertal before the first modern humans appeared in Europe. "At the time, I had no idea about the impact of my discovery," said Martisius, who is now pursuing her doctoral degree in anthropology at UC Davis. Martisius' opportunity was the result of ...

NASA sees remnants of Hurricane Manuel soaking northern Mexico, Texas

2013-09-21
Two NASA satellites observed Hurricane Manuel as it made landfall in northwestern Mexico and brought rainfall into southwestern Texas. NASA's TRMM Satellite measured Hurricane Manuel's rainfall from space and found areas where it was falling as fast as 2 inches per hour. NASA's Aqua satellite captured both visible and infrared images that revealed strong thunderstorms associated with Manuel's remnants were streaming northeast into Texas. Those rains are expected to continue to soaking central Texas through Sept. 21. As predicted by the National Hurricane Center (NHC), ...

LAST 30 PRESS RELEASES:

Thirty-year mystery of dissonance in the “ringing” of black holes explained

Less intensive works best for agricultural soil

Arctic rivers project receives “national champion” designation from frontiers foundation

Computational biology paves the way for new ALS tests

Study offers new hope for babies born with opioid withdrawal syndrome

UT, Volkswagen Group of America celebrate research partnership

New Medicare program could dramatically improve affordability for cancer drugs – if patients enroll

Are ‘zombie’ skin cells harmful or helpful? The answer may be in their shapes

University of Cincinnati Cancer Center presents research at AACR 2025

Head and neck, breast, lung and survivorship studies headline Dana-Farber research at AACR Annual Meeting 2025

AACR: Researchers share promising results from MD Anderson clinical trials

New research explains why our waistlines expand in middle age

Advancements in muon detection: Taishan Antineutrino Observatory's innovative top veto tracker

Chips off the old block

Microvascular decompression combined with nerve combing for atypical trigeminal neuralgia

Cutting the complexity from digital carpentry

Lung immune cell type “quietly” controls inflammation in COVID-19

Fiscal impact of expanded Medicare coverage for GLP-1 receptor agonists to treat obesity

State and sociodemographic trends in US cigarette smoking with future projections

Young adults drive historic decline in smoking

NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research

Chimpanzee stem cells offer new insights into early embryonic development

This injected protein-like polymer helps tissues heal after a heart attack

FlexTech inaugural issue launches, pioneering interdisciplinary innovation in flexible technology

In Down syndrome mice, 40Hz light and sound improve cognition, neurogenesis, connectivity

Methyl eugenol: potential to inhibit oxidative stress, address related diseases, and its toxicological effects

A vascularized multilayer chip reveals shear stress-induced angiogenesis in diverse fluid conditions

AI helps unravel a cause of Alzheimer's disease and identify a therapeutic candidate

Coalition of Autism Scientists critiques US Department of Health and Human Services Autism Research Initiative

Structure dictates effectiveness, safety in nanomedicine

[Press-News.org] Propofol discovery may aid development of new anesthetics