Asthma And COPD Might Be Treated By Activating Bitter Taste Receptors

Jun, 2023 - by CMI

Future therapies that stimulate the receptors for bitter taste may help those with asthma or COPD.

It's interesting to note that bitter taste receptors can be found outside of the mouth, such as in the airways. These receptors have the potential to open up airways when triggered, making them a potential treatment for asthma or chronic obstructive pulmonary disease (COPD). Researchers have created a potent and selective chemical that could open the door for future treatments in a recent study that was published in the Journal of Medicinal Chemistry of the ACS.

The TAS2R14 subtype is one of the 25 distinct types of bitter taste receptors and is most prevalent in tissues outside of the mouth. The exact composition or "ligand" in the body that triggers the receptor is unknown to scientists, who are also unsure of its shape. Nonetheless, it has been demonstrated that a number of synthetic substances, including the NSAID flufenamic acid, bind to and activate TAS2R14s.

These substances don't share any structural similarities and aren't highly potent. These issues make it difficult to create a ligand that is more powerful. Building on that research, it was necessary to create a set of TAS2R14 ligands that were even more efficient.

The researchers created numerous additional varieties based on their past discoveries that particular types of architecture boosted potency. They put these substances to the test using a cell-based technique to gauge receptor activation. This method demonstrated that a promising technique consisted of replacing a phenyl ring with a 2-aminopyrimidine and a carboxylic acid group with a tetrazole. One of the novel ligands had a potency that was six times more than flufenamic acid, requiring less of the substance to provide an effect comparable to that of the NSAID.

Also, compared to non-bitter taste receptors, this ligand was extremely selective for TAS2R14, which may help to reduce adverse effects. According to the researchers, the novel chemicals will assist clarify the mechanism, structure, and physiological role of bitter taste receptors and direct the creation of medication candidates that target them.