Scientists develop new tool to study nicotine receptors

March 27, 2018 by Anna Williams, Northwestern University
Nicotine, alternate molecular skeletal 2D rendering showing the 3D conformation of its ring at lowest energy in actual space. Credit: Public Domain

A team of scientists has developed a new technique to better understand the effects of nicotine on the brain. In a study published in Nature Methods, the investigators described the creation of a novel light-activated nicotine compound, which will allow scientists to better study receptors that play a key role in nicotine addiction.

"Investigators are now able to study the neurotransmitter receptor for nicotine in ways not previously possible," said co-corresponding author Ryan M. Drenan, PhD, associate professor of Pharmacology. "Scientists interested in studying nicotine dependence or acetylcholine—the neurotransmitter that normally binds to 'nicotine receptors'—now have a fantastic tool that, when properly employed, may enable us to uncover fundamental principles of cholinergic transmission."

Matthew C. Arvin, PharmD, a graduate student in Drenan's laboratory, was a co-first author of the study, which was conducted in collaboration with investigators at the Howard Hughes Medical Institute's Janelia Research Campus.

Photoactivatable versions of drugs, which can be activated by brief flashes of light, are an important tool used in pharmacological research to study processes in cells and to model behavior. Until recently, however, scientists lacked the ability to develop compounds for many  drugs, including a class with a so-called "tertiary nitrogen," which includes nicotine.

Credit: Northwestern University

In the current study, the team of scientists developed a new chemical method for preparing derivatives of such previously "uncageable" drugs—and applied the strategy to nicotine. After developing a photoactivatable nicotine, called PA-Nic, they utilized the compound to study .

"We used the probe to reveal new details about how chronic nicotine exposure changes the activity and location of these receptors, paving the way for a new approach to studying dependence," Drenan said.

The new strategy will be essential for studies of acetylcholine transmission and , but the approach could also be applied to other drugs that have a tertiary nitrogen, according to the authors. For example, the study demonstrates the creation of photoactivatable versions of the opioid fentanyl and the antidepressant escitalopram, among others.

"This could lead to novel research in many aspects of neurobiology that impact human health, including mood disorders or the opioid epidemic," Drenan said.

Explore further: Running away from addiction: How exercise aids smoking cessation

More information: Sambashiva Banala et al. Photoactivatable drugs for nicotinic optopharmacology, Nature Methods (2018). DOI: 10.1038/nmeth.4637

Related Stories

Running away from addiction: How exercise aids smoking cessation

December 20, 2017
New research in mice sheds light on the mechanism underlining exercise's protective effect against nicotine dependence and withdrawal.

Tiny worms may offer new clues about why it's so hard to quit smoking

November 7, 2017
Researchers at the University of Michigan Life Sciences Institute found that a previously dismissed genetic mechanism may contribute to nicotine dependence, and to the withdrawal effects that can make quitting smoking so ...

New discoveries on the connection between nicotine and type 2 diabetes

March 8, 2016
Researchers at Lund University in Sweden have made two new discoveries with regard to the beta cells' ability to release insulin. The findings can also provide a possible explanation as to why smokers have an increased risk ...

Nicotine vaccine delays the drug's effects in mice

March 9, 2016
Many people who smoke want to quit, but the urge to light up is often irresistible. An effective vaccine to help people kick the habit once and for all has been elusive. But now, scientists report in ACS' Journal of Medicinal ...

Nicotine withdrawal traced to very specific group of brain cells

November 14, 2013
Nicotine withdrawal might take over your body, but it doesn't take over your brain. The symptoms of nicotine withdrawal are driven by a very specific group of neurons within a very specific brain region, according to a report ...

Recommended for you

Scientists reverse aging-associated skin wrinkles and hair loss in a mouse model

July 20, 2018
Wrinkled skin and hair loss are hallmarks of aging. What if they could be reversed?

Breakthrough could impact cancer, ageing and heart disease

July 20, 2018
A team of Sydney scientists has made a groundbreaking discovery in telomere biology, with implications for conditions ranging from cancer to ageing and heart disease. The research project was led by Dr. Tony Cesare, Head ...

Enzyme identified as possible novel drug target for sickle cell disease, Thalassemia

July 19, 2018
Medical researchers have identified a key signaling protein that regulates hemoglobin production in red blood cells, offering a possible target for a future innovative drug to treat sickle cell disease (SCD). Experiments ...

Mice given metabolite succinate found to lose weight by turning up the heat

July 19, 2018
A team of researchers with members from institutions across the U.S. and Canada has found that giving the metabolite succinate to mice fed a high-fat diet prevented obesity. In their paper published in the journal Nature, ...

Supplement may ease the pain of sickle cell disease

July 19, 2018
(HealthDay)—An FDA-approved supplement reduces episodes of severe pain in people with sickle cell disease, a new clinical trial shows.

Scientists uncover DNA 'shield' with crucial roles in normal cell division

July 18, 2018
Scientists have made a major discovery about how cells repair broken strands of DNA that could have huge implications for the treatment of cancer.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.