NEUROPHYSIOLOGY AND BIOCHEMISTRY OF TASTE
"De gustibus non est disputandum. (There is no disputing in
matters of taste.)" This remark of Julius Caesar reminds us of the
subjectivity of taste perceptions, and the impossibility of
deciding if one food tastes better than another. This probably
reflects the modifiability of tastes, with age and state of health
of the individual, drugs recently taken, other foods with which a
given one is mixed, foods previously eaten, appetite, etc.. A
given food, or tastant does not always produce the same sensation
in everyone's mouth, or every time it is tasted. And food
preferences may change with time, so that a taste once considered
offensive (such as spinach or broccoli to many children) may
become desirable to adults.
Nature vs. Nurture in Taste Perception
This brings us to the question, are tastes acquired as a
result of various experiences during our lifetimes, or are they
innate, or "inborn"? This is addressed in Figure 1. Three
different neonates are shown, with facial expressions recorded
after placing small amounts of various solutions in the infant’s
mouth, presumably for the first time in his or her life. The first
column is the unstimulated, or "resting" face. Column 2 is the
response to distilled water (control). Column 3 is a solution of
25% sucrose; the response is described as an "expression of
satisfaction." In Column 4 a sour solution of 2.5% citric acid is
applied, resulting in pursing of the lips. Column 5 shows the
response to 0.25% quinine sulfate (bitter solution). The
expression is one of disgust; the upper lip is elevated, the
angles of the mouth are depressed, and the tongue is protruded in
a flat position, as if to expel the offending substance.
All of these reactions are somewhat typical of adult
behaviors to the same tastants, which suggests that the preference
for sweet and avoidance of sour and bitter are inborn, and not
learned. Having this ability to make judgements about tastes is
advantageous since about 10% of plants are poisonous, and those
plants also taste sour and/or bitter. Food which has decayed or
fermented also tastes sour, and smells bad as well. On the other
hand, almost all sweet-tasting plants are nutritious and nonpoisonous. Thus, the taste (or smell) of an unfamiliar food is
usually a good indicator of its nutritive value or possible danger
if consumed. It has been suggested that "gustofacial" expressions
which a baby makes like those in Figure 1 are nonverbal
communications to the mother to signal acceptance or dislike of
some food.
Probably the major sensation with consumption of food is one
of smell. For example, all meats taste salty - chicken is
different from beef or lamb only because of its odor (and its
consistency). Fruits taste sweet and/or sour - you can try this at
home: plug your nose and eat two differently flavored jelly beans;
without smell, you won’t be able to tell the difference. This
observation has led to the general rule, formulated by Haller in
the 18th century, that
FLAVOR = TASTE + ODOR
It is familiar to most of us how the enjoyment of food strongly
decreases when olfaction is impaired, as with the nasal congestion
due to a cold.
Anatomy of Taste Cells
In mammals, the physiological detection and discrimination of
various tastes occurs, in groups of cells located in the taste
buds. These are situated on the sides and in clefts of structures
known as papillae. The major types of papillae on the mammalian
tongue are shown in Figure 2. Part A shows a large fungiform (or
"mushroom-shaped") papilla surrounded by many filiform ("wireshaped") papillae. In the adult, taste buds are restricted to the
sides of the fungiform papilla, and the filiform papillae do not
have taste buds. Part B shows foliate ("leaf-shaped") papillae on
the side of the tongue. The taste buds are located in the clefts
between the papillae. In Part C a circumvallate (often called
"vallate") papilla is shown. These are found in the posterior
third of the tongue. The taste buds are located in the clefts of
these papillae, also. Most of the tastebuds are in the back of the
mouth: There are from 1 - 7 tastebuds in the fungiform papillae on
the front of the tongue and as many as 400 each in the
circumvallate papillae in the back.
Bartoshuk and her collaborators at Yale University (Reedy et
al., 1993; Bartoshuk et al., 1994) have shown that about onefourth of the population have an excess density of taste papillae
on their tongues and perceive all tastes more strongly than the
rest of us. These people are called supertasters. They also report
stronger sensations with oral irritants such as chili powder.
To see if you are a supertaster, you can perform the
following test: Dab a few drops of blue food coloring on your
tongue and swish it around. The pink circles that are exposed are
the fungiform papillae. Make round hole in a piece of paper with a
hole punch and place the paper on your tongue. (This hole is about
7 mm in diameter, and has an area of about 0.39 cm2.) People who
cannot taste the bitter compounds phenylthiocarbamide (PTC) or 6n-propylthiouracil (PROP) will have from 0-15 papillae in the
circle. Moderate tasters will have from 15-35 papillae, and
supertasters more than 35 papillae. Women are supertasters more
frequently than men, and have more fungiform papillae than men.
The structure of a single tastebud is shown in Figure 3. The
structure is about 50 m in diameter, and contains approximately
100 cells of epithelial origin, most of which extend from the base
to the taste pore, or opening into the oral cavity. It is in this
pore area that tastant molecules in the mouth presumably interact
with chemosensitive cells.
Taste buds in the front of the tongue are more sensitive to salt
and sweet stimuli and those in the back are more sensitive to sour
and bitter. However, taste buds in all areas of the mouth can
taste all of the basic tastes, and the taste buds in all areas of
the tongue are considered to be indistinguishable by light
microscopy.
The cell types in a tastebud are usually classified on
microscopic grounds as shown in Table I.
Table I. Types of cells in vertebrate tastebuds (After Kinnamon et
al., 1985 and Roper, 1989).
_______________________________________________________________
Type
Shape
Nucleus
Electron
Inclusions
density
_______________________________________________________________
I (Dark)
Long, narrow
Irregular
High
II(Light) Long, narrow
Oval
Low
III
Oval
Low
Long, narrow
Apical granules
Basal dense core
vesicles
Basal
Flat, oblate
Oval
High
Electron-lucent
and dense vesicles
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Type I cells make up about 60% of a mouse taste bud, and Type
II about 30%. Some cells with properties intermediate between
Types I and II are also seen. The dense core vesicles in Type III
cells have been suggested to have a monamine storage function.In a
study of cell lineage Delay et al. (1986) found that radioactive
thymidine was incorporated first into basal cells, then Type I
followed by intermediate cells and finally Type II cells. This
result strongly suggests that the stem cells (basal cells)
transform during their lifetimes into Type I cells, then
intermediate cells and finally Type II cells.
The lifetime of a taste cell is not very long. Beidler and
Smallman (1965) showed that the average lifespan in the rat was
about 10 days. (This compares to about 4-8 days in the surrounding
non-chemosensitive epithelium.) So there is a continuous turnover
of taste receptors, with constant replacement of synaptic
connections to the associated sensory axons. Interestingly, the
presence of sensory innervation is an absolute requirement for the
formation of tastebuds - section of a taste nerve results in
disintegration and absorption of the tastebuds, and flattening of
the papillae. If the nerve later regrows into the tongue, a
trophic factor again causes the tastebud structures to form.
Neural Pathways for Taste
From ultrastructural studies, the different cell types in
vertebrate tastebuds have been shown to be synaptically connected
as shown in Figure 4. Receptor cells (R), both Type I and Type II,
are connected to each other and to basal cells (B). Both receptor
cells and basal cells make synaptic contact with sensory axons
(A). Thus, there is a possibility of interaction between taste
cells at the receptor level, similar to the interaction between
cells in the retina. The activity of all the connected cells then
excites a sensory axon, which conducts the signal to the nervous
system.
The cranial nerves which carry taste signals are shown in
Figure 5. The anterior 2/3 of the tongue is innervated by the
chorda tympani branch of VII, and the posterior 1/3 by the IXth
nerve. Taste buds around the epiglottis are innervated by the Xth
nerve.
No afferent taste fibers are specific to any one of the socalled four basic tastes - salty, sweet, sour and bitter. Instead,
some afferents respond more strongly to one or more stimuli than
do other fibers.
The pattern of activity of thousands of such axons is decoded in
central structures to identify the tastant stimulus (see for
instance Erickson, 1963).
Some older textbooks show the sense of taste as being
represented only on the tongue.
There are also many tastebuds on the hard and soft palate
(Henkin and Christiansen, 1967).
The senses of touch, pain and temperature in the anterior 2/3
of the tongue are carried by the Vth nerve, which is also the
route of perception of irritants such as chili powder. (This is
sometimes known as the common chemical sense.) These sensations
are represented in the posterior 1/3 of the tongue mainly by the
IXth nerve and by the Xth nerve near the epiglottis.
Primary afferent nerves in the taste pathway synapse in the
nucleus of the tractus solitarius, which is also an important
sensory nucleus for swallowing (Chapter 15). Axons from cells in
this nucleus project to the ventral posterior median nucleus of
the thalamus, and then to the gustatory neocortex, as shown in
Figure 6. This is located in the portion of the postcentral gyrus
where the head is represented, near the temporal gyrus. This has
been determined from electrical stimulation of the cortex, which
results in taste sensations, and from bullet wounds which
interfere with perception of tastes.
Chemical Structure and Taste
It is generally agreed that almost everything we can taste
falls under the categories known as the four basic tastes - salty,
sweet, sour and bitter. (Some workers also describe the water
taste, or taste of pure H2O, and the metallic taste, or taste of
metals such as iron applied to the tongue, as distinct and
recognizable sensations. There is apparently also a unique taste
called umami, which is the taste of things meaty and savory.) The
fact that different compounds only produce basic-taste sensations
suggests that there are approximately four types of taste
receptors on the chemosensitive cells in the mouth (Although
recent genetic studies suggest a large multi-gene family of
receptors for bitter taste - Adler, et al., 2000). Let us briefly
consider the kinds of chemical stimuli for which each class of
receptors is specialized.
Salty
Table II shows a list of things which taste salty. The pure salt
taste is that of sodium chloride. Potassium is used as one
component of salt substitutes, but by itself has a bitter taste at
high concentrations.
Table II. Salty-tasting compounds
________________________________________________________________
General form: electrolyte
A+B-
Sodium chloride
NaCl
Lithium chloride
LiCl
Sodium bromide
NaBr
Calcium chloride
CaCl2
Ammonium chloride
NH4Cl
________________________________________________________________
Sweet
The sweet taste is more complicated, as shown by some of the
compounds listed in Table III. There is evidence that these act on
the same set of receptors, since the sweet taste of all of them is
blocked by pre-treatment of the tongue with gymnemic acid, an
extract of the plant Gymnema sylvestre (Bartoshuk et al., 1969).
This compound tastes like strong tea, and rinsing the tongue
blocks all sweet tastes for about one hour without affecting salt,
sour or bitter. The gymnemic acid occupies the sweet receptors in
the mouth, preventing other sweet-tasting compounds from
stimulating them.
Table III. Sweet-tasting compounds
________________________________________________________________
Sugars
OHC-HCOH-HOCH-HCOH-HCOH-CH2OH
Alcohols
OH-CH2-CH2-OH
Glycols
HO-C=C-OH
Saccharin
Leucine
CO
/ \ / \
|
|
N
\ / \ /
SO2
(CH3)2-CH-CH2-CH(NH2)-COOH
Lead acetate
Pb(CH3-COO -)3
Beryllium chloride
BeCl2
Aspartame
N-Aspartylphenylalanine
_______________________________________________________________
The sweet taste may be due to the formation of a double
hydrogen bond between the tastant molecule and receptor complex on
the surface of the taste cell, as shown in Figure 7. This theory
was put forth by Shallenberger (1971), and succeeded in explaining
the sweet tastes of several different compounds, some ionized and
some not. It is assumed that the tastant has a hydrogen-donating
site within 3 Ångstroms of a hydrogen-accepting site, and that
these have complementary donating and accepting sites on the
receptor membrane, also spaced 3 Ångstroms apart.
For instance, in saccharine the nitrogen atom can donate a
hydrogen ion and the oxygen can accept. Metal compounds in
solution are hydrated and in this configuration can donate and
accept H-ions.
The federal government has now recognized the carcinogenic
properties of saccharin and requires that it be labeled
accordingly. Some caution is also called for with aspartame, a
widely-used sweetener, but for a different reason: Aspartame is
composed of aspartic acid and phenylalanine, the second of which
is an essential amino acid. However, phenylalanine also is an
excitotoxin, and causes destruction of nerve cells at excessive
concentrations (Olney, 1975). In phenylketonuric babies, the
inability to metabolize phenylalanine leads to destruction of
brain tissue and mental retardation. Wurtman (1983) has shown that
the consumption of three cans of a soft drink sweetened with
aspartame can double the blood concentration of phenylalanine. It
is probably advisable to limit the amount consumed, especially by
very young children.
Sour
The sour taste is the best understood, and is due to the H+ ion
or proton. Not all acids are equally sour, but all acids taste
sour, as shown in Table IV. When the sense of smell is excluded,
equi-sour concentrations of different acids are indistinguishable.
Table IV. Sour-tasting compounds
________________________________________________________________
General form: acid
H+B-
Hydrochloric acid
HCl
Sulfuric acid
H2SO4
Nitric acid
HNO3
Acetic acid
CH3COOH
________________________________________________________________
Bitter
Finally, the bitter taste is familiar from drinks containing
quinine, and some bitter-tasting compounds are shown in Table V.
Plant alkaloids usually have a bitter taste, but so do urea and
potassium chloride. Some investigators have suggested that the
bitter taste is also stimulated by a double hydrogen-bond
mechanism, but that the hydrogen-donating site is closer to the
hydrogen-accepting site than with sweet receptors, perhaps 1.8
Ångstroms.
Table V. Bitter-tasting compounds
________________________________________________________________
Quinine
C20H24N2O2.3H2O
Caffeine
C8H10N4O2
Nicotine
C10H10N2
Urea
H2N-CO-NH2
Potassium chloride 0.1 M
KCl
________________________________________________________________
This theory can explain some interactions known to occur
between the sweet and bitter tastes: (1) After adapting sweet
receptors with strong sugar solution, distilled water has a bitter
taste. (2) Saccharin has a bitter aftertaste to many people. (3)
The dihydroxy alcohols (HO-C-C-..-C-OH) change from a pure sweet
taste with two carbon atoms between the hydroxyl groups to a mixed
sweet-bitter taste with three or four carbons, and a pure bitter
taste with five carbons. In this case, the hydrogen-donating and
accepting sites (OH) on the tastant molecule may be about 3 Å
apart in the shorter alcohol and then fall closer together with
the increased folding of the larger 5-carbon molecule.
ELECTROPHYSIOLOGY OF TASTE CELLS
Previously the term "receptor" has been applied to receptor
cells in tastebuds (cf. Figure 4). Nowadays, it is usually
restricted to mean chemosensitive groups on the surface of taste
cells. These are located in the area of the taste pore of each
tastebud, where the receptors and active ionic channels are also
found (see, for instance, Kinnamon, 1992). Taste cells have been
compared to postsynaptic nerve or muscle membranes (Roper, 1989),
because they contain active ion channels and receptors for
hormones, neurotransmitters and other dissolved substances, both
organic and inorganic.
For many years, taste cells were considered electrically
inexcitable (Tateda and Beidler, 1964; Akaike et al., 1976; Sato,
1980). This finding was probably a result of the relatively largediameter microelectrodes which were originally used to record from
the cells. When finer microelectrodes and whole-cell patch
electrodes were used, the ability of taste cells to produce
regenerative action potentials was confirmed (Roper, 1983;
Kinnamon and Roper, 1987; Avenet and Lindemann, 1987a).
More recently, the voltage-clamp method has been used to measure
ionic currents flowing across taste cell membranes during
stimulation with various compounds (Avenet and Lindemann, 1987b;
Kinnamon and Roper, 1988a; Sugimoto and Teeter, 1990). From these
studies, a clearer picture of the mechanisms of excitation by
various tastants is emerging. One apparently uniform observation
is that all of the basic-taste stimuli excite the attached sensory
axons by Ca-dependent release of neurotransmitter from the taste
cell into the synaptic cleft. How this is achieved differs from
taste cell to taste cell.
Salty
The current evidence suggests that NaCl (or another salty
compound, such as LiCl) stimulates taste cells by direct entry
through passive (ungated) channels in the cell membrane. This is
shown schematically in Figure 8, Part A. One line of work pointing
to this idea is that application of amiloride, a passive Nachannel blocker, suppresses the response of the chorda tympani
nerve to sodium applied to the tongue (Brand et al., 1985;
DeSimone and Ferrell, 1985). Amiloride also reduces the taste
intensity of Na and Li in humans (Schiffman et al., 1983). The
sodium which enters the cell presumably depolarizes it until the
threshold is reached for regenerative action potentials, which in
turn triggers an influx of calcium through voltage-gated Cachannels (Avenet, 1992).
Sweet
With sweet compounds, there are some structural similarities
which suggest that they interact with specific receptors. (Also,
the receptors are specifically blocked by gymnemic acid.) Since
most sweet stimuli are nonpolar compounds, no direct ionic
mechanism of excitation such as that for salty stimuli may be
postulated. Instead, the operation of a second messenger system is
proposed, as indicated in the following scheme (Roper, 1989):
Sweet stimulus

activates GTP-binding protein

stimulates adenylate cyclase

increases intracellular cAMP (or cGMP)

closes apical K+ channels

depolarizes taste cell

opens voltage-dependent Ca2+ channels

allows influx of Ca2+ near synapses

causes neurotransmitter release near synapses
Treatment of some cells in the mouse tastebud with sucrose causes
a depolarization and decrease in resting K-conductance (Tonosaki
and Funakoshi, 1988). Injection of cAMP or cGMP into these cells
produces the same effects. Avenet and Lindemann (1987b) also
showed that external or internal application of cAMP to frog taste
cells caused a reversible depolarization due to blockage of Kcurrents.
Sour
As shown in Figure 8, Part B, the effect of acids on taste
cells is probably to depolarize by decreasing the currents through
the voltage-gated potassium channels. It had been known for some
time that acids produced depolarizations in taste cells (Akaike et
al., 1976; Tonosaki and Funakoshi, 1984). Kinnamon and Roper
(1988a,b) showed that the acid-induced depolarization in mudpuppy
taste cells was due to a reduction in K-conductance, and the
effect was blocked by application of the K-channel blocker TEA
(tetraethylammonium.
The effect of lowering pH on single potassium channels is
shown in the next figure. This, like the salt response, is
considered a direct ionic effect on the membrane channels, not
requiring a specific macromolecular receptor.
Molecular Biology of Taste Perception
Some recent work by Margolskee and his collaborators has
shown a taste-specific G-protein in extracts of tastebud tissues.
The -subunit of the G-protein, called -gustducin, is 90%
genetically similar to transducin seen in retinal cones, and
thought to mediate light perception. The proposed function of
gustducin in taste is shown in the slide. Gustducin is stimulated
by taste stimulants binding to the receptor, and activates a
phosphodiesterase that reduces the amount of intracellular cyclic
GMP, causing the Ca-channels to open and admitting Ca, leading to
transmitter release to the attached sensory nerves.
Some of the evidence for this theory comes from knockout mice
that lack the gene encoding -gustducin. These animals can taste
salty and sour compounds but are unable to taste sweet or bitter
things. This result also shows a connection between sweet and
bitter.
Bitter
Some bitter stimuli are lipophilic and some are hydrophilic,
so they may either enter the taste cell or not. Thus, a specific
receptor may not be necessary. However, the existence of taste
blindness for certain bitter stimuli such as PTU (phenylthiourea)
may indicate some specificity of the receptor or the transduction
process (Teeter and Cagan, 1989
Zuker and colleagues (Adler et al., 2000) at UC San Diego
have identified a family of 40-80 G protein-coupled receptors
(called T2R receptors) expressed in taste receptor cells. These
are likely to be bitter taste receptors as (1) they are
genetically linked to loci that influence bitter taste in mice and
humans, and (2) mice deficient in the associated mT2R-5 gene are
poorly able to perceive bitter tastants (Chandrashekar et al.,
2000). The next figure shows calcium increases produced in cells
expressing T2R receptors in the presence of the bitter compounds
cycloheximide and denatonium.
Interestingly, T2R receptors are only expressed in cells that
contain gustducin, again suggesting a role for that G protein in
both sweet and bitter
tastes.
In the case of the bitter taste, is appears there are receptors
for many different kinds of bitter compounds, all of which taste
bitter.
_______________________________________________
While it is interesting to interpret the responses of single
taste cells to the four basic-taste stimuli, these are often
complex and the whole story is probably not as straightforward as
outlined above. In the next chapter we shall consider some
modifications of taste sensations produced by a variety of
developmental, systemic and environmental variables.