Researchers have found evidence for a potential sixth basic taste associated with the detection of ammonium chloride by the protein receptor OTOP1. This discovery could redefine our understanding of taste and its evolutionary significance.
Recent research has proposed that in addition to the familiar tastes of sweet, salty, sour, bitter, and umami, the tongue may also sense ammonium chloride as a basic taste.
Japanese scientist Kikunae Ikeda first proposed umami as a basic taste in addition to the recognized sweet, sour, salty, and bitter tastes in the early 1900s. It took him nearly 80 years before the scientific community formally recognized his proposal.
Now, scientists led by researchers in the USC Dornsaif College of Letters, Arts, and Sciences have obtained evidence of a sixth basic taste.
In a recent study published in a journal nature communications, University of Southern California Neuroscientist Emily Lehman and her team at Dorncyf discovered that the tongue responds to ammonium chloride through the same protein receptors that signal sour taste.
“If you live in a Scandinavian country, you may be familiar with this flavor and may like it,” says Lehmann, a professor of biological sciences. In some Scandinavian countries, salted licorice has been a popular candy since at least the early 20th century. The ingredients in this snack include salmiak salt, or ammonium chloride.
A thorough study of tongue reactions
Scientists have known for decades that the tongue reacts strongly to ammonium chloride. However, despite extensive research, the specific tongue receptors that respond to the tongue remained elusive.
Lehmann and his research team thought they might have an answer.
In recent years, they have discovered a protein It plays a role in sensing acidity. The protein, called OTOP1, is located within the cell membrane and forms a channel for hydrogen ions to move into the cell.
Hydrogen ions are an important component of acids, and as any gourmet knows, your tongue can sense them. acid Sour. This is why lemonade (rich in citric and ascorbic acids), vinegar (acetic acid), and other acidic foods give a tangy, sour taste when they touch your tongue. Hydrogen ions from these acidic substances travel to taste receptor cells via OTOP1 channels.
Because ammonium chloride can affect the concentration of acids, or hydrogen ions, in cells, the research team wondered if it could somehow trigger OTOP1.
Animal responses and the role of OTOP1
To answer this question, they introduced the Otop1 gene into human cells grown in the lab, allowing the cells to produce the OTOP1 receptor protein. They then exposed the cells to acid or ammonium chloride and measured the response.
“We found that ammonium chloride is a very potent activator of OTOP1 channels,” Lehmann said. “It activates as much or more than acids.”
Ammonium chloride releases a small amount of ammonia, which moves inside the cell and increases the pH, making it more alkaline. In other words, hydrogen ions are reduced.
“This pH difference facilitates the influx of protons through the OTOP1 channel,” explains Dr. Ziyu Liang. student in Riemann’s lab and first author of this study.
To ensure their results were more than just a lab artifact, they turned to techniques that simulate how nerves transmit signals and measure electrical conductivity.Using taste bud cells from normal mice and mice that the lab had previously genetically engineered Do not generate OTOP1They measured how well taste cells produced electrical responses called action potentials when ammonium chloride was introduced.
The popular Scandinavian candy Salty Licorice contains ammonium chloride, an alkaline salt, which gives the candy its unique flavor.Credit: Maxine Eschger
Taste bud cells from wild-type mice showed a sharp increase in action potentials upon addition of ammonium chloride, whereas taste bud cells from mice lacking OTOP1 did not respond to salt. This confirmed their hypothesis that OTOP1 responds to salt and generates electrical signals in taste bud cells.
This was also the case when another member of the research team, Courtney Wilson, recorded signals from the nerves that innervate taste cells. She observed that neurons responded to the addition of ammonium chloride in normal mice, but not in mice lacking OTOP1.
The researchers then went a step further and looked at how the mice responded when given the choice of drinking plain water or water spiked with ammonium chloride. In these experiments, we disabled bitter cells that also contribute to the taste of ammonium chloride. Mice with functional OTOP1 protein did not find the taste of ammonium chloride appealing and did not drink the solution, whereas mice lacking OTOP1 protein did not care about alkaline salts, even at very high concentrations. There wasn’t.
“That was really the clincher,” Lehman said. “This shows that the OTOP1 channel is essential for behavioral responses to ammonium.”
But the scientists didn’t stop there. They wondered if other animals were also sensitive to ammonium and might use the OTOP1 channel to detect it.They believe that the OTOP1 channel is part of seed It appears to be more sensitive to ammonium chloride than other species. And the human OTOP1 channel was also sensitive to ammonium chloride.
meaning of evolution
So what are the benefits of tasting ammonium chloride, and why is ammonium chloride so evolutionarily conserved?
Lehmann speculates that the ability to taste ammonium chloride may have evolved to help organisms avoid ingesting harmful biological substances containing high concentrations of ammonium.
“Ammonium is found in waste products (think fertilizer) and has some toxicity,” she explained. “So it makes sense that we evolved a taste mechanism to detect ammonium. Chicken OTOP1 is much more sensitive to ammonium than zebrafish.” We speculate that this may reflect differences in ecological niches. “Fish may simply not encounter much ammonium in the water, but chicken coops contain large amounts of ammonium that should be avoided and not eaten.”
But she says this is very early research to understand species differences in sensitivity to ammonium and why the OTOP1 channel in some species is more sensitive to ammonium and in others less sensitive. They caution that further research is needed to find out.
They have made a start towards this goal. “We identified a specific part of the OTOP1 channel, a specific amino acid, that is required to respond to ammonium,” Lehman said. “If we mutate this one residue, the channel becomes much less sensitive to ammonium, but it still responds to acid.”
What’s more, this one amino acid is conserved between different species, so there must have been selective pressure to maintain it, she says. In other words, the ability of OTOP1 channels to respond to ammonium must have been important for the survival of the animals.
In the future, the researchers hope to expand these studies to understand whether sensitivity to ammonium is conserved among other members of the OTOP proton family expressed in other parts of the body, including the gastrointestinal tract. Planning.
And who knows? Perhaps ammonium chloride joins the other five basic flavors, bringing the official number to six.
Reference: “Proton channel OTOP1 is an ammonium chloride taste sensor” by Ziyu Liang, Courtney E. Wilson, Bochuan Teng, Sue C. Kinnamon, and Emily R. Liman, October 5, 2023. nature communications.
DOI: 10.1038/s41467-023-41637-4
This research was funded by: National Institutes of Health.
