Researchers enjoy bitter taste of success

Taste has been the most elusive of the five senses. Now, genetic work is revealing how taste buds handle the chemical information that washes over them.

Bitter receptors (green) are made by the same taste cells on a rat’s tongue that make gustducin (red). Cells that make both types of protein appear yellow. Cell

Scientists from NIH and the University of California, San Diego (UCSD) describe these findings in the March 17 Cell. The report comes soon after the first identification of a functioning taste receptor. It detects umami—the meaty flavor of monosodium glutamate and parmesan cheese (SN: 1/29/00, p. 68: Available to subscribers at Meaty receptor helps tongue savor flavor).

The team looking for bitter-flavor receptors had previously found two candidates (SN: 2/27/99, p. 132: However, those proteins weren’t made by the taste cells that produce the signaling protein, called gustducin, that’s known to be important for recognizing bitterness, says Ryba. So, he, Charles S. Zuker of UCSD, and their team had to look again for the bitter receptors.

Geneticists have known for a long time that some people can taste a bitter chemical called 6-n-propyl-2-thiouracil, or PROP, while others are oblivious to it (SN: 7/12/97, p. 24: When other researchers pinpointed a region of the human genome where the gene for PROP tasting lies, the NIH-UCSD group examined the area’s DNA sequence. They found a gene there that encodes a protein similar to receptors in the nose that recognize odors.

By searching human DNA databases, the group turned up 25 similar genes. Some of these had been linked to the taste of certain bitter compounds like quinine and cycloheximide. People may have 40 to 80 genes for bitter-recognizing proteins, Ryba estimates.

Fruit flies also have a family of taste-receptor genes, Yale University researchers report in the March 10 Science.

Cells that make any of the newly found mammalian receptor proteins also produce all the others and gustducin. However, not all gustducin-producing cells make bitter receptors. Those cells may be involved in detecting sweetness, suggests taste researcher Nirupa Chaudhari of the University of Miami.

When mixed with a bitter chemical in a test tube, the receptor proteins link to gustducin to trigger the next step in taste signaling, the NIH-UCSD team finds.

“Taste is something that’s more than just a test-tube reaction. It’s a sensation,” Ryba says. “So, in the end, you have to relate everything back to an animal model.” The researchers used two strains of laboratory mice—only one of which tastes cycloheximide. Mice that perceive the chemical all have one form of a bitter receptor called T2R5, while non-tasting mice had another.

The new research gives a much more complete picture of how taste cells identify flavors, says Sue C. Kinnamon, a neuroscientist at Colorado State University in Fort Collins. “What they’ve done is a major tour de force in the field of taste,” she says.

The characterizations of the family of bitter receptors and the umami receptor have paved the way for scientists to finally understand how taste works, says Steven D. Roper of the University of Miami, a codiscoverer of the umami receptor. “We’ve finally gotten a foot in the door, and the door is starting to open,” he says.

The NIH and UCSD researchers say in their article that they hope to identify chemicals that will block bitter receptors “and in a small but significant way, eliminate bitterness from the world.”

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.