The Chemical Senses
...taste, being the lowest or least intellectual of our five senses,
is incapable of registering impressions on the mind;consequently, we cannot
recall or recover vanished flavours as we can recover, and mentally see
and hear, long-past sights and sounds. Smells, too, when we cease smelling,
vanish and return not...
W. H. Hudson, Far Away and Long Ago, 1918
Purves et al., Chapter 15 (organization somewhat odd, outline does not
This chapter has been wonderfully updated!
There is a slightly more advanced lecture on this topic, based on papers
rather than text, for my 2002 signal transduction course: Chemical
senses. The text figures referred to in that outline are to Alberts
et al. Molecular Biology of the Cell (3rd edition) Garland.
VGDethier, To know a fly, San Francisco, Holden-Day, 1962. Flies taste through
hairs on legs and are attracted to sugar accordingly.
Taste is a term applied to chemicals dissolved in water.
Many "flavors" are smell
Fig. 15.18 p. 343
Hanig (1901) - preferential localization:
sweet - tip of tongue
salt - front sides of tongue
sour - back sides of tongue
bitter - back middle of tongue
The correlation is not exclusive is not really true.
Circumvallate back of tongue
foliate sides of tongue
fungiform front of tongue
also receptors in epiglottis
Fig 15.16 & 15.18 p 343
Several types of papilla including the circumvallate papillae on the back
of the tongue, shown in this picture
from our histology course
Within each papilla are numerous clusters of cells called taste
buds shown in this histology picture. support cells, sensory cells,
and basal cells
As with olfaction, a unique feature is the turnover of receptor cells
Recent paper Note that there are genetic taste "blindnesses"
Ptc = phenylthiocarbamide, taster is dominant.
Use taste vs. non-taste to screen for G-protein coupled receptors (M. Barinaga,
Family of bitter taste receptors found, Science 287, 2133-2135, 2000)
Demonstration PTC taste test strips
Recent paper. Denis Drayna, Founder mutations. Scientific American
Oct 2005, 78-85. (There are also several letters to the editor and reply
Feb 2006, 12-14)
"...seven different forms of the PTC gene exist in sub-Saharan Africa.
But only the major taster and nontaster forms have been found...outside
of African populations."
taster detects chemicals with C=N-S
(1) taster and nontaster are ancient
(2) tasters and nontasters populated the world as in the "Out of Africa"
(3) these people did not interbreed with others (like Neanderthals).
only taster in all other primates
Recent paper U-K Kim et al....D. Drayna, Positional cloning of the
human quantitative trait locus underlying taste sensitivity to Phenylthiocarbamide,
Science 299, 1221-1225, 2003
In small area of human chromosome 7q, there are nine TRA2R (bitter taste
genes) and 7 olfactory receptor genes in this area.
PTC is 1002 bp and 1 exon
3 single nucleotide polymorphisms (SNPs) explain PTC taste insensitivity,
A49P, V262A, I296V
A colleague and friend of mine, Charles
Zuker, made important recent contributions isolation of taste receptors
T1R1, T1R2, T1R3, T2R, also the involvement of the TRP channel. Earlier,
he made tremendous contributions in Drosophila phototransduction. HHMI =
Howard Hughes Medical Institute which has helped to fund innovative and
productive scientists like Charles. There are easy to read HHMI press releases
Fig. 15.20 p. 345
generally, channel or G-protein linked receptor ultimately increasing calcium
somehow for synapse
note receptor does not have axon
Fig. 15.21AB p. 346
salt - amiloride blocked Na+ channel opens (depolarization)
sour - H+-sensitive TRP channel (PKD variant)
sweet - G-protein linked cAMP close K+ channel - depolarize
receptor is T1R2-T1R3
umami (glutamate) - and amino acids, TRPM5 channel gated by IP3 from G ...
as well as G-protein cascade receptor is T1R1-T1R3
This is very unusual! (G protein linked receptors in dimer)
Note, here is the TRP (transient receptor potential) channel again
bitter -G-protein cascade involving PLC signals through IP3 to TRPM5
or quinine sensitive K+ channel
"gusducin" (like "transducin" for vision) is term for
heterotrimeric G protein
receptor is T2R
(how selective is receptor?)
work by Carl Pfaffman, 1941, & since - receptors are not all that specific
Contradicted by very modern data supporting "labeled line hypothesis"
(well covered in book).
This applies to G protein coupled receptors, T2R1 plus T1R3 for sweet, T1R1
plus T1R3 for umami, and T2R for bitter,
Fig. 15.17 p. 342
Taste Projection (much simpler than for olfaction)
epiglottis via nerve X (vagus), circumvallate (9 of them) via IX (glossopharyngial),
others via VII (facial)
Gustatory (solitary) nucleus in medulla,
there to thalamus and then to sensory cortex
(note overlap to touch area - postcentral gyrus)
also from solitary to hypothalamus
Capsaicin (covered in the chapter on pain, Chapter 9)
for polymodal nociceptive fibers
Fig. (not in 5th edition)
Trigeminal (5) mediates irritants
chemicals (air, but definition hard for aquatic animals)
PKarlson & MLuscher, 'Pheromones': A new term for a class of biologically
active substances, Nature 183, 55, 1959 (see also J NIH Res 6, 63-66).
It is hard to imagine that something as fundamental as pheromones was not
even a word before 1959
Box 15B pp328-329
pheromones - vomeronasal organ. For insects, there are many variations,
but the most famous are sex attractants from female moths detected by feathery
antennae on male moth. (Here,
from my "butterfly" collecting days, is a male luna moth.) Usually
it is a simple molecule like a 10 carbon acetate. It can attract male from
a few miles who flies upwind at first. Pheromones have been used to trap
Fig. (not in 5th edition)
There are unusual primaries like aromatic and putrid , there may be many
primaries, although mixtures give a single perception confounding the ability
to define primaries
Relative to other senss, receptors difficult to stimulate
Perhaps more than with the sense of touch, olfaction is related to motivational
The sense of smell is especially important in other animals (dogs)
Fig. 15.7A p. 331
Anatomy of olfactory epithelium.
Note: the receptors are neurons
Receptors turn over (this is unusual), as noted by dividing stem cell and
developing (immature) receptor, since cells are very exposed (to dry air,
pathogens, etc.). New cells must establish connections.
There are also sustaining cells
Fig. 15.8 p 332
Receptors are ciliary with "9 + 2" arrangement of microtubules
as seen structurally.
Cilia are in mucus
slowly adapting (receptors) even though it seems otherwise (processing)
Fig. 15.11A p. 336
Transduction - G protein coupled receptor via adenylate cyclase
There is a specialized olfactory alpha subunit of the G protein (Golf)
Na+ - Ca2+ channel is like that of photoreceptor in that cAMP acts as a
ligand to open the channel from inside the cell
Ca2+ opens Cl- channel
there is also a pathway involving PLC and IP3, but which is otherwise similar
in the background, there is a Na+/Ca++ exchanger
Fig. 15.9A p. 333
G-protein coupled receptor is very variable (there may be thousands, meaning
that olfactory receptors contribute predominantly to diversity of G-protein-coupled
receptors) and has specific variable regions.
Reflection In the early 1990's, olfactory receptors were found to
be G protein coupled receptors, and there are lots of olfactory receptors;
Richard Axel and Linda B. Buch won the 2004 Nobel
prize for this work. I see from my alumni magazine that Axel was class of
67 at my college (Columbia College) while I was class of 69. He kept working
there (at the med school) and joins 70 from Columbia to get the Nobel Prize,
19 in Physiology and Medicine. I followed the link suggested by my alumni
magazine and found this.
G. Barnes, S. O'Donnell, F. Mancia, X Sun, A. Nemes, M. Mendelsohn, and
R. Axel, Odorant Receptors on axon termini in the brain, Science, 304, 1468,
Each cell expresses only one type of receptor.
Seemingly randomly arranged on olfactory epithelium.
Axons of axons with same receptors converge at glomeruli.
The same receptors are used in axon guidance.
D-J Zou et al., Postnatal refinement of peripheral olfactory projections,
Science 304 1976-1979, 2004.
"A hallmark of mature glomeruli is that they are innervated exclusively
by axons from olfactory sensory neurons expressing the same olfactory receptor."
(summary of above)
Here they show:
(1) Glomeruli start our heterogenious and the frequency of heterogenious
glomeruli decreases with development.
(2) Sensory stimulation contributes to the final unique mapping.
Fig 15.9B p. 333
number and organizations of genes and proteins in C. elegans, Drosophila,
Note, no introns in mammals
Fig. (not in 5th edition)
distribution of genes in human, many on 11
Fig. 15.14D p. 338
Glomeruli - > Mitral cells -> lateral olfactory tract (stria)
Also Periglomerular cells and Granule cells for processing
There is specificity of projection (space) of specific odorants to olfactory
bulb favoring labeled line scheme of processing
Fig. 15.1 A - D
Olfaction is a complex sensory system in part because of the CNS projection
to amygdala, and, via pyriform cortex, to thalamus, hypothalamus, amygdala
and entorhinal cortex (and even to higher areas, hippocampus, orbitofrontal
cortex) , areas involved in "emotion" (Chapter 29)
Test questions from 2005 - 2012 relating to this outline
For cAMP in olfactory receptor cells, answer either (1) What enzyme makes
it? Or (2) What does it do?
adenylate cyclase, gates a sodium-calcium channel
Say something relating the richness of human olfactory sensation and how
it is related to the diversity of G protein coupled receptors.
substantial richness is mediated by nearly 1000 different GPCRs
In the sense of taste, for sweet and for amino acids, what was unique about
the G protein coupled receptor?
it is a dimer
Regarding IP3 for umami and bitter taste receptor cells, answer either (1)
What enzyme made IP3? or (2) What is the type of channel gated by IP3?
PLC, for calcium
In addition to the 5 primaries for taste stimulation, with input via cranial
nerves VII, IX an X, it is argued that stimulants like capsaicin contribute
to our overall appreciation of gustation. Answer either (1) Which cranial
nerve is used? Or (2) What is the term for the receptor type?
5 trigeminal, polymodal nociceptive
"Three SNPs associated with PTC insensitivity: A49P, V262A, I296V."
Translate either (1) SNP, (2) PTC or (3) A49P, V262A, I296V.
single nucleotide polymorphism (genetic change), a bitter chemical tastant
for which there are tasters and non-tasters (based on a gene) in humans,
the number is the amino acid position - the first letter is the normal amino
acid, the second letter is what it is changed to
What kind of molecule (e.g. enzyme, pump, heterotrimeric G protein) are
- Answer for either of these molecules involved in taste transduction: (1)
T1R2, or (2) TRPM5?
G protein coupled receptor, channel
In an adult human, a new olfactory receptor cell is "born." How
does it "decide" which glomerulus to connect to?
based on the G protein coupled receptor it binds to, it connects to a glomerulus
collecting information from receptors expressing the same receptor molecule
Answer either (1) How did cAMP get to be higher after an odorand binds the
receptor molecule? Or (2) What does that cAMP do to change the cell's electrical
the alpha subunit of the G protein (Golf) activates adenylyl cyclase, it
is the ligand for a calcium channelSuppose your research isolated the receptor
molecules for putrid and aromatic. Answer either (1) Characterize these
molecules molecularly. Or (2) How do they differ from eachother?
G protein coupled receptors, their sequences are different especially in
Relative to visual and auditory receptor cells, what is the notable difference
in the life expectancy of olfactory (and gustatory) receptor cells?
Taste and smell receptor cells die and get replaced
In what way does the cAMP made by adenylate cyclase under the command of
Golf function like cGMP in rod cells?
It is a ligand affecting the channel from inside the cell
Taste projected near to where the tongue's somatosensory representation
was on cortex. Relate this to the situation for olfaction.
smell, by contrast, projects to a deep, dark, mysterious assortment of places,
the limbic system
What is the significance of a comparison of PTC sensitivity alleles in primates,
people of sub-Saharan Africa, and all other people?
that polymorphism originated early but after primates, but only people with
taster and non-taster came out of Africa to populate the world
For the TRPM5 channel used in taste, answer either (1) what flows through
this channel? or (2) What is the ligand for this channel?
calcium ions, IP3
Relative to all the other G protein coupled receptors we have discussed
in this course, what is unusual about the ones for sweet and umami?
they are dimers
For taste, give the name of the nucleus or the location of nucleus that
feeds to the VPM (ventral posterior medial) nucleus of the thalamus.
solitary nucleus in brainstem
Here's a partial list of nerves that carry taste and spice information from
the mouth: V, IX, & X. Give the name or number of the one I left out.
What does "trp" stand for when applied to channels?
transient receptor potential
What type of molecules are the two components of the dimer (T1R1 + T1R3)
used for umami?
G protein coupled receptor
What type of molecule is gusducin and what cell is it in?
G-protein of taste cell
Why is it important for all the types of taste cell transduction mechanisms
to ultimately increase intracellular Ca2+ concentration?
must release transmitter vesicles
Linda B. Buch and Richard Axel won the 2004 Nobel Prize for discovering
the nature of the olfactory receptor. What type of molecule is it?
G rotein coupled receptor
Why do male moths have more elaborate antennae than females?
to detect sex attractant pheromones from female
What is the organelle responsible for chemoreception in an olfactory receptor
What are the 9 big papillae at the back of the tongue called?
In what way are the G protein coupled receptors unusual for sweet and umami
this is the only time they have been mentioned as being dimers
Bigger than a taste bud, what is the term for the bump that is visible on
the surface of the tongue?
Histology of the olfactory epithelium shows mitoses and developing cells
(as well as mture receptor cells). What does this mean, regarding receptor
maintenance, also true for taste but different for vision and audition?
cells turn over, old ones die, new ones replace them
In olfactory transduction, cAMP is made by adenylate cyclase. What does
this cAMP do?
In contrast with somatosensation, vision and audition, with respective primary
cortical projections, what is the situation for higher projection in olfaction?
to limbic system
All the olfactory receptor cells that synapse into one glomerulus have something
in common. What?
use same G protein coupled receptor
What is the significance of the solitary nucleus in the medulla?
synapses for taste
Bitter stimulation, or stimulation with amino acids, activates PLC (phospholipase
C) to create IP3. In this example, the IP3 activates a different Ca2+ channel
than the IP3 receptor of the endoplasmic reticulum. Give the name or location
of this channel.
TRPM5 in plasmalemma
The facial (7), glossopharyngeal (9) and vagus (10) nerves carry standard
taste information. What additional nerve carries information from polymodal
nociceptive receptors responsive to capsaicin?
Relative to gustation (taste) how many primaries (different receptor types)
are there for olfaction (smell)?
many more (500-1000)
There's a Na+/Ca2+ channel in olfactory receptors like the one in rod cells
(that one gated by cGMP). What gates the olfactory receptor channel?
"A hallmark of mature glomeruli is that they are innervated exclusively
by axons from olfactory neurons expressing the same olfactory receptor."
What kind of molecule is this receptor?
G protein coupled receptor
Many genes for olfactory receptor molecules are found in clusters on the
human chromosomes. How did they come to be near each other?
a gene gets duplicated and its neighboring twin can evolve to take on new
"The olfactory projection is more complicated than those of other senses."
Name one of the many targets beyond the olfactory bulb.
pyriform cortex, olfactory tubercle, amygdala, entorhinal cortex, orbitofrontal
cortex, thalamus, hypothalamus, hippocampal formation
Return to Syllabus
Return to Stark home page
This page was last updated on 3/9/12