Friday, October 29, 2010

Take the bitter pill. How an accidental discovery may make asthma a thing of the past.

A new paper published by Nature Medicine has found that your lungs contain taste receptors, and they can specifically sense bitterness!

Dr. Stephen B. Liggett MD, a pulmonologist at University of Maryland School of Medicine, and his team of researchers discovered the bitter taste receptors (TAS2Rs) by accident while studying human airway smooth muscle (ASM) receptors. What's even more surprising is that the TAS2 receptors found in the lung's smooth muscle cells are identical to those found on your tongue. There are a few exceptions of course; the lung's taste receptors are not grouped together like they are in the tongue (better known as taste buds), and they have no sensory link to the brain, which explains why you can't taste awful bitterness every time you travel to a very polluted city and simply inhale.

The leading theory on the evolution of sensing bitter substances was always thought to relate to poisons. Our ancestors would have been exposed to a multitude of natural bitter-tasting plant toxins that could potentially have killed them if ingested, the ability to taste something bitter and spit it out served them well in their survival. It was because of this that Dr. Liggett and his team initially thought the receptors in the lungs would react to bitterness  in a similar way, by stimulating the body to remove the substance through violent coughing and contraction of the airways. However, when they tested various bitter substances known to stimulate TAS2Rs on mice, they found that the complete opposite occurred. The airways ended up dilating extensively, up to three times more than standard bronchodilator treatments!

Substances such as Quinine, a drug that has been successful in the control and treatment of malaria, is now being considered for the treatment of obstructive airway diseases like asthma, simply because it's also very bitter tasting and it appears to stimulate TAS2Rs because of this. Current treatments for asthma and other restrictive and obstructive lung disease base their mode of action on airway dilation either by stimulating certain receptors (B2 agonists) that cause the airways to dilate, or by decreasing lung inflammation (various corticosteroids). These treatments are effective but many also have extensive side effects due to their impact on other parts of the body. B2 receptors are found in your blood vessels and intestinal tract, as well as in your airways. The US FDA even banned two drugs, Serevent and Foradil, both short-acting B2 agonists, after finding out that they increased the severity of asthma attacks when taken without corticosteroids. The importance of the TAS2Rs could mean that drugs could be localized to cause dilation of airway smooth muscles, and do nothing else! This all equates to minimal short and long term side effects with vastly improved efficacy.

As of 2009, asthma affects about 300 million people worldwide, so chances are that you know someone personally affected by it. I remember once having to help someone with a very severe asthma attack that didn't have their medication with them, and then watching them go from collapsed, on-the-floor and unable to breathe to fine and dandy within less than a minute once she received a few puffs of a B2 agonist. The sight was almost miraculous! To think that asthma may be treated far more effectively with something as simple as a bitter-tasting substance simply is simply astonishing, it really showcases what modern science and research can develop.

My grandmother had very serious asthma all her life, requiring several inhalers throughout her life. If she knew what kind of potential treatments they would develop for her condition she probably wouldn't have believed it. Yet what these scientists are doing is helping millions, and it was all because of an accidental observation while toying around with mice. Pretty impressive if you ask me.

Go read the original article at Nature Medicine:
http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2237.html

Or read more about the banning of specific bronchodilators by the FDA over at:
http://www.nytimes.com/2008/12/12/health/policy/12fda.html?ref=health

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