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 follow chapter).
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.

Taste (Gustation)

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)
" 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
They suggest
(1) taster and nontaster are ancient
(2) tasters and nontasters populated the world as in the "Out of Africa" hypothesis
(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 here.

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)

Fig. 15.21CD
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 ... cascade
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

Fig. 15.18E
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

Trigeminal chemoreception

Capsaicin (covered in the chapter on pain, Chapter 9)
for polymodal nociceptive fibers

Fig. (not in 5th edition)
Trigeminal (5) mediates irritants

Smell- Olfaction

chemicals (air, but definition hard for aquatic animals)

Landmark paper:
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 pests.

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 "affect"
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.

Recent work
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, 2004
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.

Recent work
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, mouse, human
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 potential?

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 particular locations
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.

VII facial

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 cell?


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 tastes?

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?

gate channels

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 function

"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

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