T2R22 Activators

Chemical activators of T2R22 can induce intracellular signaling pathways that lead to the perception of bitterness. Capsaicin, a compound known for its pungency in chili peppers, acts on T2R22 by activating TRPV1 channels. This activation can increase intracellular calcium levels, which in turn can trigger the signaling cascade involving T2R22. Similarly, quinine, a naturally occurring compound, activates T2R22 by engaging with G-protein-coupled receptors that are part of the receptor's signaling mechanism. This interaction prompts a conformational change that activates the receptor. Denatonium benzoate, one of the most bitter substances known, activates T2R22 by binding to its extracellular domain. This binding event leads to a conformational alteration in T2R22, initiating the signaling process that results in bitter taste perception.

In addition to these, several sweeteners and other bitter compounds have been identified as activators of T2R22. Sucralose, despite being a sweetener, can interact with and activate T2R22, leading to the sensation of bitterness. Caffeine, widely consumed for its stimulating effects, indirectly activates T2R22 by modulating cAMP levels through its action on adenosine receptors, which can influence T2R22 signaling pathways. Similarly, saccharin and acesulfame potassium, both artificial sweeteners, can directly activate T2R22, resulting in bitter taste transduction. Other compounds such as PTU, naringin, aloin, phenylthiocarbamide, and magnesium sulfate also bind to T2R22, inducing structural changes that activate the receptor. For example, PTU interacts with the active site of T2R22, naringin and aloin bind directly to the receptor, phenylthiocarbamide activates T2R22 through direct interaction, and magnesium sulfate engages with the receptor's external domain, all leading to the activation of the receptor and subsequent bitter taste signaling.