Vertebrate chemoreception

Smell (olfaction)

traditional knowledge

Smell- Olfaction chemicals (air, but definition hard for aquatic animals) - Complex
unusual primaries like camphoraceous, musky, ... pungent and putrid
many primaries, receptors difficult to reach, in nasal epithelium
the idea is that there would be receptor molecules that bind odorants which fit:
J.E.Amoore et al. The stereochemical theory of odor, Scientific American, Feb. 1964
interestingly, though it seems to be a forgotten field, Amoore studied human anosmias -- there are specific genetic smell-blindnesses
receptors are ciliary and their cilia have "9 + 2" microtubules- histology
these cells are unusual in that they turn over
7 transmembrane domain receptor
channel is like that of photoreceptor
vomeronasal organ snake tongue olfaction, hamster sex pheromone

A small reference to recent research:
L. Stowers et al., Loss of sex discrimination and male-male aggression in mice deficient for TRP2, Science, 295, 1493-1500, 2002
mice engineered to lack this "transient receptor potential" (see invertebrate phototransduction lecture) channel lack expression in the vomeronasal organ and lack pheromonal detection for male discrimination of females as well as for male-male aggression.

The news of cloning of olfactory receptors:
M. Barinaga, How the nose knows: Olfactory receptor cloned, Science 252, 209-210, 1991

new work

Diego Restrepo et al., Second messenger signalling in olfactory transduction. J. Neurobiol. 30, 37-48, 1996
TRANSPARENCY of olfactory neuron and transduction mechanism
like Fig 22-18 on p. 1156 which covers how basal (stem) cell -> neuron
(not many neuron types "turn over," needs to make new connections)
Fig.: note that the gCa(L) is voltage-dependent and gK(Ca) is Ca dependent
there is a sodium-calcium antiport
cAMP -> Ca2+ influx -> Cl- channel
IP3 ->Ca2+ channel in plasmalemma which opens nonspecific cation and K+ channel

H. Breer et al., Molecular genetics of mammalian olfaction, Behavior Genetics 26, 209-219, 1996 on reserve
(this is an easy-to-read paper)
Olfactory marker protein (OMP) 19 kDa 162 a.a. but big mRNA with 1600 untranslated
upstream binds Olf-1 (olfactory factor)
expressed in mature neurons
OBP odorant binding protein19kDa homodimer in mucus
like lipocalins: serum retinol binding protein and hamster urinary "aphrodisin"
Golf is sort of like a Gs; there is a specific adenylate cyclase (type III)
nonspecific channel most like that of photoreceptor
(similar mechanism - gating from internal cyclic nucleotide)
the IP3-gated channels have properties like endoplasmic reticulum IP3 receptor-channel
receptor - minimal in that loops are small and thus like opsin,
TRANSPARENCY lots of variability in transmembrane spans #4 & #5
900-950 bp intronless gene, come in clusters
20 in 400 kb on 17p, also on human chromosome #19
by contrast, in immune system, somatic DNA is rearranged to give diversity, but not in olfaction
TRANSPARENCY - expression
each cell expresses one or several, and arranged in spatial clusters
control of expression will be the next big question. Olf-1 is helix-loop-helix factor

TRANSPARENCY Fig. 2 (Molday 1996) elaborates on the olfactory transduction pathway through Golf to AC to cAMP which opens CNG channel causing an influx of Ca2+. Calcium ions further activate a Cl- channel reinforcing the depolarization. But Ca2+ also feeds back by binding calmodulin to activate cAMP PDE

Taste (gustation)

I corresponded with Dr. Lindemann who has an interesting site about taste.

Traditional knowledge

Taste [on tongue] 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
Papillae -> taste buds. 1 & 2 support, 3 sensory, <- 4 basal
Unique feature: turnover of receptor cells
Gustation - chemicals - Many "flavors" are smell
dissolved in water

According th Lindemann, the following dogma is not quite true:
sweet - tip of tongue - cAMP close K+ channel - depolarize
salt - front sides of tongue - amiloride blocked Na+ channel
sour - back sides of tongue - pH sensitive K+ channel
bitter - back middle of tongue - K+ Channel or PLC
note that there could be different molecular receptors on one cellular receptor:
some people are taste "blind" for PTC=phenylthiocarbamide
TT and Tt genotypes are tasters

New work

D. W. Tingley, Transduction in the retina is also a matter of taste (research brief), The Journal of NIH Research 7 (October 1995) 44-48
(review of recent work by Margolskee et al. and the discussion which arose)
TRANSPARENCY - bitter in circumvallate papillae
Use bitter tasting chemical denatonium but others like quinine may be different
earlier found gusducin, now transducin, the two are 80% homologous at amino acid level
transducin activates taste specific phosphodiesterase,
but, unusually, channels are probably blocked by cyclic nucleotides
questions still to answer
what are the receptor molecules?
do transducin and gusducin work in the same cells?
how do IP3 and cyclic nucleotide pathways relate?
what are differences between different taste primaries?
how do different species relate? (frog not respond to sweet)
G.T.Wong et al., Transduction of bitter and sweet taste by gusducin, Nature 381, 796-800,
knockout mice for alpha subunit shows same one used in bitter and sweet

Fig. 1 a (Kinnamon and Margolskee 1996) shows taste stimuli, at the apical surface, can interact through channels or via receptors and second messengers. Ultimately, channels on the basolateral surface are affected, with the calcium channel being involved in transmitter release.

Fig. 1 b details these mechanisms for channels:
(1) salt is via a sodium channel blocked by amiloride
(2) acid is by:
(i) a proton blocked potassium channel
(ii) an amiloride blocked sodium channel which is carrying protons
(iii) a proton gated cation channel
(3) bitter is by quinine or divalent ion blocked potassium channel

Fig. 2 (Kinnamon and Margolskee 1996) elaborates the mechanisms involving receptors signalling through second messengers (as well as additional channel-mediated tastes)
(1) amino acids:
(i) the metabotropic glutamate receptor is for umami
(ii) the arginine indirect cation mechanism is for catfish
(2) sweet:
(i) amiloride blocked cation channel
(ii) AC mechanism
(iii) PLC mechanism
(for ii and iii, phosphorylation of potassium channel, channel closes, cell depolarizes)
(3) bitter:
(i) PLC
(ii) PDE mechanisms

Recent advances:

C. Holden, A taste for MSG (random samples) Science 287 799, 2000,
umami is like brain glutamate receptor except less sensitive

M. Barinaga, Family of bitter taste receptors found, Science 287, 2133-2135, 2000.
Start with tasters vs non-tasters ofPROP, locate mutation, look for G protein coupled receptors.
Find family of about 50, overlap in cells that use gusducin

RJDavenport, New genes may be key to sweet tooth, Science 292, 620-621, 2001
Till now, sweet receptor was elusive. It's a G protein-coupled receptor.
Using tasters and non-tasters (genetic difference in mice), a chromosomal region was identified.
Then looking at the corresponding area in the human genome, the gene expressed in taste cells was found.

References:

J.E.Amoore et al. The stereochemical theory of odor, Scientific American, Feb. 1964
This page was last updated on September 27, 2000

M. Barinaga, Family of bitter taste receptors found, Science 287, 2133-2135, 2000.

M. Barinaga, How the nose knows: Olfactory receptor cloned, Science 252, 209-210, 1991

H. Breer et al., Molecular genetics of mammalian olfaction, Behavior Genetics 26, 209-219, 1996

RJDavenport, New genes may be key to sweet tooth, Science 292, 620-621, 2001

C. Holden, A taste for MSG (random samples) Science 287 799, 2000

Kinnamon, S. C., and R. F. Margolskee, 1996 Mechanisms of taste transduction. Curr Opin Neurobiol. 6: 506-13.

Molday, R. S., 1996 Calmodulin regulation of cyclic-nucleotide-gated channels. Curr Opin Neurobiol. 6: 445-52.

Diego Restrepo et al., Second messenger signalling in olfactory transduction. J. Neurobiol. 30, 37-48, 1996

L. Stowers et al., Loss of sex discrimination and male-male aggression in mice deficient for TRP2, Science, 295, 1493-1500, 2002

D. W. Tingley, Transduction in the retina is also a matter of taste (research brief), The Journal of NIH Research 7 (October 1995) 44-48

G.T.Wong et al., Transduction of bitter and sweet taste by gusducin, Nature 381, 796-800

This page was last updated March 20, 2002

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