ATP is key taste messenger

New evidence discredits previous assumptions that assigned the role to serotonin

By | December 2, 2005

Adenosine triphosphate (ATP) has outshined serotonin as the most likely key neurotransmitter passing on the sense of taste from taste bud cells to primary afferent gustatory nerve fibers, researchers report in this week's issue of Science.

"It's the first time that we are able to find, at the level of these synapses, a substance that fills all the criteria of a neurotransmitter," co-author Leslie Stone, from Colorado State University in Fort Collins, Co., told The Scientist. "This doesn't rule out the involvement of serotonin or other substances in the taste bud, we just believe they're acting at another level, probably in the crosstalk between cells."

The cellular and molecular mechanisms of how chemical stimuli -- such as sugars, acids, and salts -- are converted into electrical signals are still widely unknown. Taste cells communicate with themselves through chemical and electric synapses, and some also communicate with nerves afferent to the central nervous system. Several known neuromodulating substances - serotonin, glutamate, acetylcholine, ATP, peptides - have been identified inside the buds, but none unambiguously pinpointed as a transmitter that acts between taste cells and neurons.

Past experiments have pointed to serotonin as the most likely candidate, suggesting it might act on afferent nerves through its 5-HT3 receptors. "It wasn't proved - it was only inferred," Scott Herness from the Ohio State University College of Dentistry, in Columbus, Oh., who did not participate in the new study, told The Scientist. "It was assumed that serotonin was involved between taste cells and nerves - nearly dogma."

But in new experiments steered by Thomas Finger from the Rocky Mountain Taste and Smell Center, 5-HT3 knock-out mice discriminated between tastes as easily as wild-types, suggesting serotonin is not, in fact, the key neurotransmitter. "Now we need to go back and rethink the role of serotonin in taste buds," said Herness.

To demonstrate ATP's involvement, Finger and his team studied mice with silenced P2X subunits, or ATP receptors present on the nerve fibers. They recorded neural responses to chemical stimulation of the oral cavity in both P2X knockouts and wild-type mice, and found that silencing the ATP receptors specifically eliminates taste response in nerve cells. In a set of behavioral experiments, knockout mice were seriously handicapped relative to wild-types when discriminating between sweeteners, glutamate, and bitter substances. An in vitro bioluminescent assay also showed that taste cells release ATP when stimulated by taste.

More work has to be done, and these results do not rule out the possibility that serotonin or other transmitters could still work in conjunction with ATP on afferent neurons, according to Stephen Roper, of the University of Miami School of Medicine in Miami, Fl., who did not participate in the study. "Finger's team knocked out one specific type of serotonin receptor. There might very well be other types of receptors involved that we haven't yet identified," he told The Scientist.

Roper also cautioned against drawing simplified assumptions from knockout experiments. "The absence of signal when you knock out a receptor clearly demonstrates that receptor's key role, but it doesn't rule out the involvement of other transmitters," he said. "The analogy is one of a three legged stool -If you knock out one of the legs, the stool falls. But does that mean the other legs weren't supporting the stool?"

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