The Salty and Burning Taste of Capsaicin

The tongue is a kind of funny organ. From a physiological point of view, you can place solutions on the tongue that will be toxic to most any cell, and the tongue will give information, in a hopefully reversible manner, about the solution’s chemical composition and whether it should be ingested. Remember the first time that you had a drink of vodka or scotch? It really burned. Do you know the reason for this? It turns out that neurons in the mouth, including the tongue, that carry nociceptive (tissue damaging) information contain receptors belonging to the transient receptor potential vanilloid (TRPV) family. The most investigated of these TRPV receptors is TRPV1. One reason TRPV1 is so extensively studied is that it is activated by capsaicin (CAP), the principle component in chili pepper that gives it its spicy or pungent taste (Caterina et al., 1997). It is also activated by acid and heat having a threshold temperature of 42 C. Previous studies on nociceptive neurons that innervate the face and mouth, as well as TRPV1-expressing HEK293 cells, showed that TRPV1 channels responded to ethanol in a concentrationdependent manner (Trevisani et al., 2002). Specifically, ethanol potentiated the response of TRPV1 to CAP and protons and lowered the threshold for heat activation of TRPV1 from 42 C to 34 C, which is near the temperature of the tongue. This provides a likely mechanistic explanation for the ethanol-induced sensory responses that occur at body temperature and for the sensitivity of inflamed tissues to ethanol, such as might be the case in esophagitis, neuralgia, or wounds (Hirota et al., 2003). For us gourmands, however, these data help rationalize why the pungent sensation of spicy food increases when we drink alcohol. Given the temperature dependence of TRPV1 receptors, the pungency should be reduced if one has a cold beer rather than some heated brandy. For many years it has been known that ethanol also produces taste (as opposed to painful) responses (Hellekant, 1965; Sako and Yamamoto, 1999). However, the molecular and cellular mechanisms regarding the transduction mechanisms remain unknown. In a series of papers, Vijay Lyall and colleagues have identified the presence of a TRPV1 variant in taste receptor cells (Lyall et al., 2004, 2005a,b,c). From the above discussion, it should not be surprising that they found this receptor to be also sensitive to ethanol. They also found that this receptor has other important functions in gustatory physiology. Specifically, in the presence of salt, it is responsible for the amiloride-insensitive salt taste. They also found that the application of just ethanol causes a transient decrease in the volume of taste receptor cells and produces responses in taste cells and tastesensitive neurons. Note that these results were obtained with a 20% vol/vol ethanol solution, which is 3.43 M. At the very minimum, this should serve as a warning to all of us who dissolve chemicals in hyperosmotic solutions containing ethanol (or DMSO) and add them to cells. Below we present background information to lead you through these two papers by first reviewing some of the basic anatomy and physiology of the peripheral gustatory system and then showing how they relate to measurements of properties of taste cells from fungiform papillae and recordings from gustatory neurons from the chorda tympani branch of the facial nerve. We then review briefly the methodology and guide readers through these long and detailed articles. Taste receptor cells (TRCs) in taste buds from fungiform papilla synapse with chorda tympani (CT) neurons (Finger and Simon, 2002). Taste buds are comprised of 50–100 taste receptor cells that extend from the taste pore, which is in direct contact with tastants placed in the mouth, to the basement membrane that separates the epithelium from the papillary layer. Taste cells comprise a simple epithelium that is embedded in a protective stratified epithelium. The tight junctions that are located beneath the microvilli (that project into the taste pore) serve to make this a polarized epithelium and protect the basolateral surface from the various solid and liquid foods that are placed in the mouth. Taste cells are frequently exposed to highly nonisotonic solutions (water, vodka); they can reversibly respond to the resultant volume flux changes because of the small surface area of taste cells that are exposed to the external solutions (Holland et al.,