Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Communication Routes within the Taste Bud by Neurotransmitters and Neuropeptides
College of Dentistry, Ohio State University, 305 W. 12th Avenue, Columbus, OH 43210, USA
Correspondence to be sent to: Scott Herness, e-mail: herness.1{at}osu.edu
Key words: gustation, neuromodulation, neurotransmission, sensory processing, sensory transduction, taste
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Introduction |
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 Top Introduction Serotonin as a paracrine...Cholecystokinin as a peptide...ConclusionsReferences |
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Taste receptor cells (TRCs) are located throughout the oral cavity, sequestered into morphological structures known as taste buds. These differentiated epithelial cells relay the presence of tastants to the central nervous system via sensory afferent nerves. Only a minority of TRCs within the bud synapse with these nerve fibers. This anatomical finding has lead to the dichotomization of TRCs into ‘true’ TRCs and supporting cells. However, this original conception—that a single TRC is excited by a tastant molecule and releases neurotransmitter onto its postsynaptic afferent nerve fiber—has been undermined by more recent physiological and molecular findings. For example, a single neurotransmitter, as might be expected from this scheme, has not been observed. Rather, there is evidence for at least five neurotransmitters within the mammalian taste bud: glutamate, serotonin, norepinephrine, acetyl choline and GABA. Additionally, TRCs expressing essential transduction molecules such as gustducin and members of the T2R family are not synaptically connected to the CNS. How then do TRCs equipped to respond to stimuli communicate with the central nervous system? The cloistering of TRCs into the precisely arranged structure of the bud may provide a clue. The bud, a highly conserved morphology of the vertebrate gustatory system, is an obvious substrate for cell to cell communication. Hence, alternative signaling pathways, such as paracrine communication, could explain this paradox. Rather than acting as arbitrarily collected detectors, TRCs within the bud may operate as a unit. Our investigations of neurotransmitters and neuropeptides in rat circumvallate and foliate TRCs have elucidated new pathways of communication among TRCs. Two, serotonin and cholecystokinin, are described here.
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Serotonin as a paracrine signaling agent in taste buds |
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TopIntroductionSerotonin as a paracrine...Cholecystokinin as a peptide...ConclusionsReferences |
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One of the best studied neurotransmitters in the vertebrate taste bud is serotonin (5HT). Anatomical studies localize serotonergic TRCs to a subset of type III cells (the TRCs which form synapses with the afferent nerve); however, less is known of its physiological role(s). Since it is assumed to be one of the transmitters between the TRC and the afferent nerve, it was somewhat surprising when TRCs (rather than the afferent fiber) were demonstrated to be responsive to serotonin. In particular, calcium-activated potassium current and voltage-dependent sodium current were both inhibited by micromolar concentrations of 5HT (Herness and Chen, 1997
, 2000). Pharmacological exploration suggested this effect to be mediated
by 5HT1A receptors; 8OH-DPAT, a specific 5HT1A agonist, mimicked
this effect, whereas phenylbiguanide, a 5HT3 agonist, was without effect. To
further explore the expression of serotonergic receptors in taste buds, an RT–PCR
survey was conducted using gene specific primers against fourteen receptor subtypes
(5HT1A, 5HT1B, 5HT1C, 5HT1D,
5HT1F, 5HT2A, 5HT2B, 5HT2C, 5HT3,
5HT4, 5HT5A, 5HT5B, 5HT6, 5HT7).
The mRNA of two—5HT1A and 5HT3—was observed to be expressed in
taste buds (Kaya et al.,
2004). Immunocytochemistry using 5HT, 5HT1A, or 5HT3
specific antibodies was employed to examine the pattern of their cellular expression.
Whereas 5HT and 5HT1A immunoreactivity was observed in TRCs, 5HT3
immunoreactivity was not. Instead, 5HT3 immunoreactivity was observed in
neural elements with the dermal core of the papillae, but not within the taste bud. These
data are in agreement within other studies which have demonstrated a subset of
5HT3 positive neurons in the petrosal ganglion, where the cell bodies of these
afferent fibers are located (Wang et al.,
2002). On the other hand, using an antibody specific for 5HT1A
receptors, a distinct subset of TRCs were labeled. Immunocytochemical double labeling
experiments subsequently demonstrated that 5HT-expressing and 5HT1A
receptor-expressing TRCs are non-overlapping populations (Figure
1, top panel), hence establishing a
serotonergic paracrine pathway among TRCs of the bud.
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Collectively, these observations suggest that serotonin plays a more complex role than originally imagined. We suggest there is local circuitry within the bud; release of serotonin may simultaneously act to excite the afferent nerve via 5HT3 receptors while inhibiting a subpopulation of TRCs via the 5HT1A receptors.
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Cholecystokinin as a peptide signaling agent in the taste bud |
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TopIntroductionSerotonin as a paracrine...Cholecystokinin as a peptide...ConclusionsReferences |
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In addition to classic ‘small molecule’ neurotransmitters, TRCs have more recently been demonstrated to express neuropeptides. These include vasoactive intestinal peptide (VIP; Herness, 1989
), cholecystokinin (CCK;
Herness et al., 2002),
neuropeptide Y (NPY; personal observations) and somatostatin (SST; personal
observations). Peptides often co-localize with classic small molecule neurotransmitters
and act, through specific peptide receptors, as neuromodulators that accentuate the
effect of the classic neurotransmitter at higher stimulus intensities.
CCK, the best studied peptide in TRCs, is distributed in a subset of TRCs throughout
the oral cavity (Herness et al.,
2002). Its expression, evidenced by immunocytochemistry, was verified with
mRNA expression using RT–PCR on isolated taste buds. These results suggest that CCK
in TRCs may be regulated differently than other cells of the body, with robust peptide
expression but low levels of mRNA expression. To examine function, physiology experiments
were conducted using patch clamp analysis and fura-2 calcium imaging techniques on
dissociated rat posterior TRCs. Three major physiological actions in response to
micromolar concentrations of CCK (CCK-8, sulfated) were observed—inhibitions of two
types of potassium current (delayed-rectifier and inward-rectifier) and increases of
intracellular calcium. These physiological effects would act in concert to place the cell
into a more excitatory state. They were blocked by proglumide, a non-specific
CCK-receptor antagonist, lorglumide, a specific antagonist of the CCK-A receptor, but
were unaffected by L-365,260, a specific CCK-B blocker, pharmacologically demonstrating
their mediation by a specific peptide receptor. In a separate physiology study using
calcium imaging, CCK-responsive TRCs were demonstrated to be bitter responsive and
respond to ACh (Lu et al.,
2003). These physiological investigations were followed up by
immunocytochemical studies. In one, a significant number of CCK-expressing TRCs
(
60%) co-expressed gustducin. In another study, CCK-A receptor expression was
observed in a subset of individual TRCs within the taste bud. In double labeling
experiments using CCK and CCK-A receptor antibodies, the surprising result was obtained
that there is almost complete overlap of these two subpopulations of cells (Figure
1, bottom panel). This co-distribution
pattern indicates that CCK operates in an autocrine manner in the taste bud.
Taken together, a unifying picture of the action of cholecystokinin in the taste bud is emerging. We hypothesize that CCK acts as an autocrine agent to potentiate the excitatory actions of tastants on TRCs. When sufficiently excited by a tastant, an individual TRC releases CCK which, via CCK-A receptors, intensifies the underlying physiological response via changes in electrical excitability and increases of intracellular calcium. It is possible that CCK may be involved in bitter transduction since CCK-expressing TRCs are bitter sensitive and also significantly co-express gustducin.
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Conclusions |
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TopIntroductionSerotonin as a paracrine...Cholecystokinin as a peptide...ConclusionsReferences |
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Although the possibility of cell-to-cell communication in the taste bud has been often raised, it is only recently that discreet signaling pathways have been elucidated. One question–how TRCs expressing tastant receptors yet lacking neural innervation communicate with the central nervous system–is being addressed by advances in our understanding of expression patterns of neurotransmitters and neuropeptides within the taste bud. Two examined in this communication, serotonin and cholecystokinin, represent previously unrecognized paracrine and autocrine routes, respectively. Other neurotransmitters–norepinephrine, acetyl choline, glutamate–will likely have similar though still undiscovered roles. Ultimately, elucidating the expression patterns of neurotransmitter and neuropeptide receptors will be required to understand the pathways of information processing within the taste bud.
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References |
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TopIntroductionSerotonin as a paracrine...Cholecystokinin as a peptide...ConclusionsReferences |
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Herness, M.S. (1989) Vasoactive intestinal peptide (VIP)-like immunoreactivity in rodent taste cells. Neuroscience, 33, 411–419.[CrossRef][Web of Science][Medline]
Herness, S. and Chen, Y. (1997) Serotonin inhibits calcium-activated K+ current in rat taste receptor cells. Neuroreport, 8, 3257–3261.[Web of Science][Medline]
Herness, M.S. and Chen, Y. (2000) Serotonergic agonists inhibit calcium-activated potassium and voltage-dependent sodium currents in rat taste receptor cells. J. Membr. Biol., 173, 127–138.[CrossRef][Web of Science][Medline]
Herness, S. Zhao, F.L. Lu, S.G., Kaya, N. and Shen, T. (2002) Expression and physiological responses of cholecystokinin in taste receptor cells. J. Neurosci., 22, 10018–10029.
Kaya, N., Shen, T., Lu, S.G., Zhao, F.L. and Herness, S. (2004) Expression and localization of serotonin receptor subtypes in rat taste buds. Am. J. Physiol. Regul. Integr. Comp. Physiol., 286, R649–R658.
Lu, S.G., Zhao, F.L. and Herness, S. (2003) Physiological phenotyping of cholecystokinin-responsive rat taste receptor cells. Neurosci. Lett., 351, 157–160.[CrossRef][Web of Science][Medline]
Wang, Z.-Y., Keith, I.M., Olson, E.B., Vidruk, E.H. and Bisgard, G.E. (2002) Expression of 5-HT3 receptors in primary sensory neurons of the petrosal ganglion of adult rats. Autonom. Neurosci., 95, 121–124.[CrossRef][Web of Science][Medline]
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