Not only are there more than four tastes, but several types of bitterness have been discovered.
IN 1995 THE PHYSIOLOGY OF SMELL took a great step forward with the identification of the proteins that constitute the receptors of nasal olfactory cells. However, the receptors of the papillary cells in the tongue and mouth that are sensitive to taste remained unknown. These gaps are gradually being filled. Alejandro Caicedo and Stephen Roper at the University of Miami have shown that the human gustatory system is capable of distinguishing several sorts of bitter taste.
In 2000, the same biologists who five years earlier had discovered families of olfactory genes found a vast family of receptors for what was then thought of as a single bitter taste. Other teams went on to show that individual receptors react selectively to compounds of a particular sort of bitterness. In parallel with this research it became apparent that each taste receptor cell expresses several RNA messengers, which in turn code for several receptors. It seemed natural, then, to suppose that individual receptor cells react to two or more taste compounds.
Neurological and behavioral studies conducted with rats, monkeys, and human subjects indicated that these different species are able to distinguish between several bitter stimuli. What is the cellular basis for this ability? Do taste receptor cells react specifically to one stimulus or to several? Progress in answering these questions was slow because ongoing neurophysiological investigation pointed to a variety of sources of interference along the nerve pathway that leads from the gustatory papillae to the brain.
Caicedo and Roper attacked the problem with a new imaging method that showed, in situ, the activation of taste receptor cells by a stream of calcium ions. A coloring agent sensitive to such ions was injected into the cells using a micropipette, and the reactions of the cells to various stimuli were observed while the distribution of these calcium ions was measured in real time with the aid of a laser, which excites the coloring agent, and a confocal microscope, which makes it possible to observe deep tissue cells. The University of Miami biologists were thus able to examine the reaction of several hundred taste receptor cells to a series of bitter compounds.
Cycloheximide was found to trigger strong but transient variations in the concentration of calcium ions in taste receptor cells. The four other molecules tested—denatonium benzoate, sucrose octaacetate, phenylthiocarbamide, and quinine—produced weaker but prolonged reactions lasting several minutes. The intensity of the reaction in each case depended on the concentration of the molecules to which the cell was exposed, which varied for each type of molecule. What is more, the recorded results corresponded to the behavioral response of rats fed with solutions of these bitter molecules (which act only above a certain threshold concentration).
Five Types of Bitterness
After meticulous study the Miami researchers established that only 18% of the 374 cells tested reacted to one or more of the five bitter compounds when they were administered at moderate concentrations. Among the cells that were sensitive to bitter compounds, reactions varied: 14% of the cells reacted to cycloheximide, 4.5% to quinine, 3.7% to denatonium benzoate, 2.4% to phenylthiocarbamide, and 1.6% to sucrose octaacetate.
The total proportion of taste receptor cells that register bitterness in the gustatory papillae (which contain other kinds of cells as well) turned out to be comparable to the proportion of cells sensitive to bitterness in the restricted population of taste receptor cells tested. None of the papillae studied seems specific to bitterness, and both the proportion and the distribution of cells sensitive to bitterness are comparable to those of the RNA messengers of receptors for bitter molecules. The Miami studies showed once again, only this time at the cellular level, that the different parts of the tongue are not specific to particular tastes, contrary to a view widely held among cooks and gourmets.
Applying the five stimuli to each cell in turn, Caicedo and Roper observed that a majority of the cells sensitive to bitterness reacted only to one of the five compounds tested, with their neighbors reacting to different ones. One quarter of these cells were activated by two bitter compounds, and 7% reacted to more than two of the five compounds. Note that these reactions were independent of one another: Stimuli were not simultaneously administered to a given taste receptor cell, and higher concentrations of bitter molecules did not increase the proportion of bitter-sensitive cells.
The sensitivity of individual cells to specific kinds of bitterness—obviously it will no longer do to speak of bitterness as though it were a single thing—would explain the observed behavioral reactions and, in particular, the capacity to make sensory distinctions between different sorts of bitterness. The nerve fibers that go out from cells specific to a given kind of bitterness appear to be grouped in dedicated bundles that communicate with a particular area of the brain.
It remains to come up with names for the various bitter tastes that are now known to exist.