Taste Receptors In Lungs May Help Asthmatics

Writing in Nature Medicine, researchers report on discovering bitter taste receptors in human lungs, and that bitter compounds expand airways in asthmatic mice. Stephen Liggett talks about the possibility of treating asthma and chronic obstructive pulmonary disease with bitter compounds.

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JOE PALCA, host:

This is SCIENCE FRIDAY from NPR. I'm Joe Palca. Ira Flatow is away.

A lot of times the scientific process is a long, plodding journey following little breadcrumbs of information one at a time until you've built a more solid case for how the universe was born or how our brains work.

But once in a while that incremental process leads to something totally out of left field, just plain weird, opening up new paths to explore.

And that's what happened in the case of my next guest, who found something unexpected in our lungs: bitter taste receptors, same kind as you have on your tongue, a discovery that the researchers say may someday lead to new treatments for respiratory ailments like asthma. That research appears in the journal Nature Medicine.

But let's back up a second. Why even look for taste receptors in the lungs? And do we really need new treatments for asthma, or are the ones we have today just fine?

That's what we'll be talking about. So give us a call. Our number is 800-989-8255. That's 1-800-989-TALK. If you're on Twitter, you can tweet us your question by writing the @ sign followed by scifri. If you want more information about what we'll be talking about this hour, go to our website at www.sciencefriday.com, where you'll find links to the topic.

So let me introduce my guest. He's Steve Liggett, a professor of medicine at the University of Maryland School of Medicine in Baltimore. He joins us by phone. Welcome to SCIENCE FRIDAY, Dr. Liggett.

Dr. STEPHEN LIGGETT (University of Maryland): Thank you, how are you doing?

PALCA: I'm great. So I presume you werent looking for taste receptors in the lung. How did you happen to find them?

Dr. LIGGETT: Well, we utilized one of the modern techniques that arose from the Human Genome Project, called a micro-array test, looking for all possible genes that are expressed in human airways' smooth muscle because we felt that we had a lack of information about what receptors might be utilized either for therapy or to help us understand why the airways close down in an asthma attack.

PALCA: Maybe we could take a step back. What is a receptor, a taste receptor in this case?

Dr. LIGGETT: Well, receptors in general are molecules - proteins, actually -that sit on the cell surface, typically, and they receive either something made in the body or something that's given to the body, and that is typically called an agonist, and that sits on the receptor and then activates some intercellular pathway.

PALCA: So the bitter taste receptors on our tongue, when something bitter floats past them, they tell the nerves to fire, and the firing goes to the olfactory part of the brain that deals with smell, and we smell - or we taste something bitter.

Dr. LIGGETT: That's correct, and it is actually thought that they evolve to protect us against eating plant-based toxins because most toxic plants are very bitter.

PALCA: Okay, so what are these things doing in the lung?

Dr. LIGGETT: Well, I can tell you what they do. I can speculate on what they might be there for, you know, from an evolutionary standpoint. Maybe we should start with the first part first.

PALCA: Okay.

Dr. LIGGETT: Which is the exciting, therapeutic part. So we found out of the 25 different known bitter taste receptors, we found 17 of them expressed on the muscle that surrounds the bronchi, which are the tubes that conduct the air through the lung to the peripheral(ph) of the lung for gas exchange.

And that was, in and of itself, sort of like a piece of light that we just didn't even expect to see. And I think a lot of times people would just sort of let that go as either an artifact or some vestigial sort of evolutionary thing that maybe it has no relevance anymore.

PALCA: Right.

Dr. LIGGETT: But we decided to go for it because, you know, there's just a dearth of new therapies and a dearth of understanding about asthma in general. So we took a look, and it turns out that these receptors stimulate calcium in the cell, and we had this expectation that they would constrict the airways, but they actually open the airways better than any known drug ever used for the treatment of asthma.

PALCA: Wow, and so what's happening is when something stimulates these receptors, they're allowing the lungs to relax?

Dr. LIGGETT: That's correct actually, the airways to relax, which opens them. And in asthma - an asthma attack or asthma exacerbation, whatever you want to call it, is due to the constriction of this smooth muscle and an inability to move air, and patients will describe it feeling like they're breathing through a straw.

PALCA: Right. So I'm curious. If the bitter taste receptors on your tongue are there to warn you that something bad is coming into your mouth that might be toxic, what would the bitter taste receptors in the lung do when something harmful came into the lung? It sounds like dilating wouldn't you know, making it easier to breathe might not be the best strategy.

Dr. LIGGETT: That's exactly right, and we were on the track that you were thinking about, that these would be alarm-type receptors that might make you cough or something like that and escape the noxious environment. But that's not what we see.

And we have one explanation that seems very strong, and that is that bacteria make a bitter taste substance, and so if you have a serious bronchitis or a pneumonia, the substance that's being created by the bacteria opens the airway to help you clear that pneumonia and the cellular debris that occurs from the pneumonia, you know, sort of chewing away at your airway. So that may have been why they evolved, is to protect us from serious pneumonia and bronchitis infections progressing.

PALCA: I got it. Okay, all right. Well, interesting. Let's take a call now and go to Deborah(ph) in St. Louis, Missouri. Deborah, welcome to SCIENCE FRIDAY. You're on the air.

DEBORAH (Caller): Yeah, hi. How would this relate to the fact that I'm allergic to sweet smells like air fresheners and things like that?

PALCA: Huh, okay. Deborah, thanks for that call. What about that?

Dr. LIGGETT: Well, I mean, we have little understanding of all the different triggers for asthma. But we did happen to look, as part of this sort of new idea about taste receptors being on the lung, for the sweet receptors, which there are some known sweet receptors as well, and we didn't find any. So I don't have a good explanation for her symptoms.

PALCA: Uh-huh. Okay, so how would you use this information to make new products, new treatments?

Dr. LIGGETT: Well, I think we're an unusual situation. If you look at a lot of other fields, such as you know, I think cancer is a good example, where a new pathway is found that might have a real strong therapeutic value, and the problem is you usually have maybe one or two drugs that act on that pathway, and you're kind of stuck with, well, now what do we do?

In this case we know that there are at least 10,000 naturally occurring substances that come from certain vegetables and trees and other plants or synthetic substances that are actually used to treat other disease that are already known, that activate these receptors.

So we've got sort of a different situation. We've got a large number of possible treatments, and we just need to find the best ones that, you know, are the most potent, and they're palatable and don't have any side effects.

So this puts us, I think, on a little bit faster track than perhaps finding a novel pathway with hardly anything to work with. Does that make sense?

PALCA: Yeah, I think so. But what I want to clear something up, because these patients with asthma, their lungs are working, it's just that they - the muscles around them constrict inappropriately and make it hard for them to breathe.

Dr. LIGGETT: Yes, and that difficulty in breathing is not we shouldn't trivialize it, because in essence what has what has happened is in our young children, we're seeing an epidemic of asthma and obesity together because it's so difficult for them to breathe that they don't exercise.

And in older adults its, you know, it ultimate causes them not to be able to sleep, and then, you know, there's lost productivity from work. And the medicines that are used in the hospitalizations alone account for about $23 billion a year in health care costs. So it is a major problem for the 20 million asthmatics that we have.

PALCA: Okay. Let's take another call now and go to Tanya(ph) in Madison, Wisconsin. Tanya, you're on the air.

TANYA (Caller): Hi, so this is kind of funny. I'm a hops engineer for MillerCoors.

PALCA: Hops?

TANYA: And in the hops, the profile that creates a bitterness is alpha and beta acids. And I was curious whether or not something like, almost like a spray version of these alpha and beta acids could be sprayed into the lungs to stimulate the receptors and if maybe that was the chemical or one of the chemicals at some point that were used to find to find this finding in the first place.

PALCA: Hmm. Interesting question. Dr. Liggett, what about that?

Dr. LIGGETT: Well, I didn't quite understand what - the name of the compounds that she was talking about. Did you?

PALCA: She called them alpha and beta acids.

Dr. LIGGETT: I'm not sure. Maybe it was essence. I'm not sure.

PALCA: Yeah.

Dr. LIGGETT: So...

PALCA: Yeah, but this is this is the substance, hops, that gives beer its bitter taste.

Dr. LIGGETT: Yes. So I would tell you that sometimes the, what we perceive of as being bitter may not actually be a bitter taste receptor agonist. So we'd have to separate that out first.

But then secondly, she's right. She hit on a very important point, and that is that we believe that the best way to give this drug is by an aerosolarized form, in an inhaler so that they can go directly into the lungs, right onto the airways, rather than a pill or a liquid, where we don't feel that you would be really able to achieve the concentrations necessary to activate enough receptors to get the therapeutic effect.

PALCA: Right, right. So is there any I can't think of it, but is there any implication from this finding about why asthma seems to be on the increase?

Dr. LIGGETT: No, probably not. I mean, I can tell you what we think about that.

PALCA: Sure.

Dr. LIGGETT: It may be, you know, multiple possibilities. First of all, we know there's genetic links. And we don't really have much control over who, obviously, mates with who in order to, you know, ultimately produce additional children. So we have some parent sort of selection.

There's not much selection pressure against that anymore, like there might have been, you know, long ago. And so we have that issue.

The environmental issue is a big deal also because allergies to cockroaches and dust and certain pollens, and cats, for example, are some big ones. And in the lower socioeconomic groups, you would be surprised at what you, you know, what can be found in substandard housing. So that is a potential problem.

PALCA: Yeah, okay.

Dr. LIGGETT: And then finally, you know, we've shown in others that infection with the human rhinovirus causes about 50 percent of asthma exacerbations, and as we continue to have schools like we do, we're going to have, you know, continued common cold.

PALCA: Okay, Dr. Liggett, we have to leave it there, I'm afraid. Thank you. It's an interesting finding you've made.

Stephen Liggett is a professor of medicine at the University of Maryland School of Medicine in Baltimore. Thanks for joining us.

Dr. LIGGETT: Thank you.

PALCA: And after this break, we'll talk about your genome and what you can learn from it. So stay with us.

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