Monday October 25 2010
Existing asthma inhalers work by relaxing the muscles surrounding the narrowed airways
“Human lungs can ‘taste’ bitter substances in the air,” reported The Independent. It said a study has found that taste receptors have been discovered in the smooth muscle that controls the flow of air into the bronchi, the narrow airways of the lungs. The researchers claim that the findings could lead to new types of drugs for asthma sufferers.
This research was a laboratory study in human cells and mice, looking at the effect of ‘bitter tasting’ inhalants on newly discovered ‘bitter taste receptors’ in the smooth muscle of the airway.
The discovery of receptors that appear to be involved in the constriction and relaxation of airway muscle is an important avenue for future research. It is possible that it may one day lead to new treatments for asthma. This is very early research, however, and much further investigation is needed before it is known if a treatment will come from this.
Where did the story come from?
The study was carried out by researchers from the University of Maryland School of Medicine and the Johns Hopkins Bloomberg School of Public Health. The research paper states that funding was provided by US National Heart, Lung and Blood Institute grants. The study was published in the peer-reviewed medical journal Nature Medicine.
The newspapers have generally covered the research well, although the focus on lungs being able to ‘taste’ bitter substances is an unusual interpretation. The research was not really about taste. Instead, it examined the effects at cellular level of stimulating the newly discovered receptors in the smooth muscle of airways, and the mechanisms behind the observed dilatation of these airways (bronchodilation).
What kind of research was this?
The researchers say that there is an ongoing effort to find new treatments for asthma and COPD that may act on the underlying mechanisms that maintain the tone of the muscle in the airway. They say that the majority of illnesses and deaths in people with these conditions are caused by airway obstruction, partly due to restriction/constriction of the smooth muscle of the bronchi. Many existing therapies aim to relax this tissue, opening the airway. To date, a key avenue of research has focused on receptors called the G protein-coupled receptors (GPCR), which are involved in the regulation of the tone of airway muscle. But there are likely to be other mechanisms.
In this study, the researchers discuss a new set of receptors that they discovered in human airway smooth muscle cells, and which are similar to the bitter-taste receptors on the tongue. They investigated the effects of different substances on these receptors in cultured human and animal cells, and in live mice. Their aim was to determine whether these receptors also regulated airway tone.
What did the research involve?
There were several parts to this study. The first part was in human cells grown in the laboratory. The researchers took human airway smooth muscle (ASM) cells and exposed them to substances that elicit a taste response, including substances known to stimulate sweet and bitter taste receptors. They observed what effect this had on the cells, particularly on the concentration of calcium ions.
They then investigated whether these effects would be seen in isolated mouse airways (airways removed from the body). Here, the researchers wanted to see whether the airways would constrict when exposed to these substances. These experiments on intact mouse airways were also repeated on portions of non-diseased human bronchi. Further experiments were then conducted to determine exactly how the bitter taste receptors caused relaxation in the smooth muscle of the airway.
In a final step, the researchers determined the effects of inhaled bitter tastants (substances that stimulate bitter taste receptors) on sedated, intubated mice that had allergic airway inflammation or hypersensitive bronchi. These responses were compared to the mice’s response to albuterol, a bronchodilator that relaxes muscles in the airways and is commonly used to treat asthma symptoms in humans.
What were the basic results?
Cultured cells that were exposed to the chemical substances reacted similarly to the way cells behave in the lead up to bronchoconstriction (constriction of the airways), i.e. there was an increase in the concentration of calcium ions inside them.
In the intact mouse airways, however, exposure to bitter tastants (such as chloroquine, denatonium and quinine) caused relaxation, while acetylcholine and serotonin resulted in contraction. In general, bitter tastants led to relaxation. In human bronchi, chloroquine or saccharin induced a 50-80% reduction in tension of the airway.
When live, intubated mice with inflamed or hypersensitive airways were exposed to inhaled bitter substances, there was more relaxation in the airways than with albuterol.
How did the researchers interpret the results?
The researchers say that they have shown that substances that bind to bitter taste receptors cause bronchodilation of intact airways and that the effect is greater than that of current asthma treatments.
They note that there are a number of non-toxic, synthetic chemicals that may have these effects and are potential therapeutic options for airway diseases such as asthma.
This animal and laboratory research has identified and profiled the action of some bitter taste receptors in the smooth muscle of the airways. The researchers speculate as to why they are there. They suggest that it may be an evolutionary protective mechanism against the airway closure that could happen as a result of infection with certain bacteria that cause bronchitis and pneumonia, and which release bitter substances.
The discovery of receptors that appear to be involved in the constriction and relaxation of airway muscle is an important avenue for future research. It is possible that it may one day lead to new discoveries and treatments for asthma and chronic obstructive pulmonary disease. This is very early research however, and much further investigation is needed before it is known if a treatment will come from this.