Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Nicotine receptors found for the first time in the mouth open the door to new treatments

20.01.2009
* Gabinete de Planeamento, Estratégia, Avaliação e Relações Internacionais / Ministério da Ciência, Tecnologia e Ensino Superior

A research team by scientists in Portugal and the US has found for the first time nicotine receptors in the taste buds. In fact, although most of the toxicity of smoking is linked to other components, it is nicotine that leads to smoking addiction and until now it was believed that this substance had to migrate into the brain – where its specific receptors existed - to provoke its effects.

This new discovery published in the Proceedings of the National Academy of Sciences (PNAS) reveals a second recognition pathway most probably contributing for addiction and suggesting a possible new target for anti-smoking drugs. The added bonus is that on this route the drugs can be applied topically (on the tongue), drastically reducing their side effects. This novel pathway is also shown to activate a brain area that when damaged can lead to instant loss of smoking addiction suggesting that mouth nicotine receptors can play a key role in the whole dependence process.

Tobacco addiction produces devastating health problems including high number of premature deaths in long-term smokers, half of these occurring as early as middle age. Specific problems include cardiovascular diseases and cancer, but also increased risk of infection such as tuberculosis, insulin resistance and diabetes, healing difficulties as well as reproductive problems and can even lead to infertility. Despite this, just in the United States, 45 million adults smoke and even if numbers are slowly diminishing in developed countries, rates continue to increase in developing countries where as much as 40% of the population can smoke. This while we know that, at least in developed countries, a large percentage of these smokers want to give up but is simply incapable of doing it.

This irresistible power of tobacco, or more exactly, of nicotine, resides in its effect on the brain. Smoke inhalation results in nicotine being transported into the lung from where it enters the blood circulation and is carried into the brain. There it binds nicotinic cholinergic receptors (nAChRs) and ultimately leads to the release of “feel good” neurotransmitters, such as dopamine. The problem is that long-term exposure to nicotine leads to an increased number of nicotine receptors in the brain and eventually tolerance to dopamine. This means that when we stop smoking other stimulus are not sufficient to produce enough dopamine to induce sensations of pleasure, and a general state of “unhappiness” - so well known to those trying to stop the habit – occurs. Withdrawal symptoms include restlessness, anxiety, concentration problems and, of course, a constant craving for tobacco.

Other factors such as culture or even habits of association such as “a coffee and a cigarette” contribute to the whole pattern of addiction. Drugs to combat smoke addiction interfere with the nicotine receptors in the brain, while slowly desensitising the individual to dopamine but, not only they carry a multitude of side effects, such as severe depression, but also have reduced success rates with only about 20% of people remaining smoke-free on the long-term. Recently, widespread prohibition of smoking in public spaces was hoped to affect smoking numbers but results, so far, are not very promising highlighting the urgency for new strategies to combat the problem.

It is in this context that Albino J. Oliveira-Maia, Jennifer R. Stapleton-Kotloski, Miguel A. L. Nicolelis, Sidney A. Simon and colleagues at the Medicine Faculty and the Institute of Cellular and Molecular Biology in the University of Porto, Portugal; Virginia Commonwealth University, Virginia, USA; Duke University Medical Center, North Carolina, USA; and the Edmond and Lily Safra International Institute for Neuroscience of Natal, Rio Grande do Norte, Brazil, decided to look into a recently described mouse lacking a protein - called TRPM5 - linked to the recognition of bitter tastes (nicotine is known to be bitter) since previous research have suggested that taste is important for tobacco addiction. In fact individuals with an extreme capacity to taste bitterness are more resistant to smoke addiction, while lesions to the insula – a brain area where the gustatory cortex is localised – can affect smoking addiction.

To the researchers’ surprise, when comparing normal animals against animals lacking TRPM5 in the presence of nicotine and quinine (that also has a bitter taste) solutions, it was discovered that, although incapable of tasting bitter tastes, Trpm5 negative animals could still distinguish nicotine from water and, more surprisingly, also from quinine. These results suggested a second pathway of recognition- which is TRPM5 and taste independent - for nicotine in the mouth.

And in fact, further studies in rats revealed the existence of nicotine receptors in the Taste Receptor Cells and taste nerves of the mouth, which, when triggered by nicotine, activated the gustatory cortex with a very different neural pattern from the one obtained by the recognition of pure bitter taste, like in quinine case. However, when nicotinic cholinergic receptors (nAChRs) inhibitors – used to stop smoking - were put on the tongue, both the behavioural and neural effects of nicotine became similar to those obtained with quinine.

What Oliveira-Maia, Simon and colleagues’ results reveal is that nicotine stimulates two systems in the mouth, one related to TRPM5, which is also used to recognise other bitter substances such as quinine, and a second one apparently specific for nicotine and Trpm5 independent. This last recognition system leads to an unique neural activation pattern of the gustatory cortex probably linked to nicotine addiction. The clue to this resides in the fact that damage in the brain insula area – where the gustatory cortex is – can eliminate any addiction to tobacco even in chronic smokers using several packets a day just before the injury. If the mouth nicotine receptors are confirmed to be linked with these insula effects, blocking them can turn out to be "the" weapon against smoking.

Either way, Oliveira-Maia and colleagues’ discovery raises the possibility of, not only using anti-smoking drugs topically avoiding in this way many of the side effects seen when the drugs are used sistemically, but also, by creating a second front of attack, contributing to more efficient anti-smoking therapies crucial in a world where smoking still kills more than 5 million people a year worldwide.

Piece by Catarina Amorim (catarina.amorim at linacre.ox.ac.uk)

Catarina Amorim | alfa
Further information:
http://www.pnas.org/

More articles from Health and Medicine:

nachricht Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>