Scientists claim ‘serendipitous’ discovery of bitterness blocking compound

In the study​, the researchers described how probenecid, an FDA-approved treatment for gout, can inhibit bitterness perception by acting on a subset of bitter taste receptors. They claim that the discovery could help ensure better nutrition for those who reject bitter foods, and could also contribute to therapeutic compliance, particularly for children.

Senior author Paul Breslin, a sensory biologist at Monell said: "Bitter taste is a major problem for pediatric drug compliance and also for proper nutrition, such as eating those healthy but bitter green vegetables. But we currently have very limited ways to effectively control bitter taste."​

The study’s authors said they discovered probenecid’s bitterness blocking property by accident, in the course of a collaborative project intended to better understand the structure and function of TAS2Rs, a group of about 25 different bitter taste receptors. They were using probenecid to prevent the outflow of calcium-sensitive fluorescent dyes in a study of bitter taste receptor signaling, and found that it unexpectedly inhibited activation of one of the target bitter taste receptors in response to the bitter compound salicin.

In a series of in vitro ​studies, the researchers found that probenecid does not physically block the interaction of bitter molecules with the taste receptor’s primary binding site; instead, it seems to bind elsewhere on the receptor, thereby modulating the receptor’s interaction with bitter molecules.

Integral Molecular senior author Joseph Rucker said: "Probenecid's mechanism of action makes it a useful tool for understanding how bitter receptors function. This knowledge will help us develop more potent bitter taste inhibitors."​

The researchers then undertook a series of human sensory studies, and found that probenecid “robustly inhibited”​ perception of salicin’s bitterness.

"This demonstrates how we can take in vitro experiments and go on to show how they make a difference functionally and perceptually,"​ said Breslin.

Monell and Integral Molecular researchers said that further sensory studies would help determine whether the inhibitory effect of probenecid works with other TAS2R taste receptors.

Source: PLoSONE​ (2011)

doi:10.1371/journal.pone.0020123

“Probenecid Inhibits the Human Bitter Taste Receptor TAS2R16 and Suppresses Bitter Perception of Salicin”​

Authors: Greene TA, Alarcon S, Thomas A, Berdougo E, Doranz BJ, et al.