Abstracts - Association for Chemoreception Sciences

#57 SYMPOSIUM:
THE NEW ‘FACES’ OF CHEMOSENSATION —
UTILIZING CHEMOSENSORY SIGNALING
PATHWAYS OUTSIDE THE CANONICAL
CHEMOSENSORY ORGANS
Genetics of the bitter taste receptor T2R38 underlie
susceptibility to upper respiratory infection
Noam A. Cohen 1,2 , Robert J. Lee 1 , Danielle R. Reed 3 , Peihua Jiang 3 ,
Gary K. Beauchamp 3
1
University of Pennsylvania/Otorhinolaryngology - Head and Neck
Surgery Philadelphia, PA, USA, 2 Philadelphia VA Medical Center/
Surgery Philadelphia, PA, USA, 3 Monell Chemical Senses Center
Philadelphia, PA, USA
Innate and adaptive defense mechanisms protect the respiratory
system from attack by microbes. Here, I describe our recent
studies that demonstrate that the bitter taste receptor T2R38
is expressed in the human upper respiratory epithelium and is
activated by acyl-homoserine lactone quorum sensing molecules
secreted by Pseudomonas aeruginosa and other gram-negative
bacteria. T2R38 regulates human upper airway innate defenses
through nitric oxide production, resulting in stimulation of
mucociliary clearance and direct antibacterial effects. Moreover,
common polymorphisms of the TAS2R38 gene are linked to
significant differences in the ability of upper respiratory cells
to clear and kill bacteria. Lastly, TAS2R38 genotype correlates
with human sinonasal gram-negative bacterial infection. These
data suggest that T2R38 is an upper airway sentinel in innate
defense, and that genetic variation that contributes to human
individual differences in ability to taste phenylcarbamide (PTC)
and related molecules also contributes to individual differences
in susceptibility to respiratory infection. Acknowledgements:
P30DC011735 R01DC004698 P50DC000214 R01DC010842
#58 SYMPOSIUM:
THE NEW ‘FACES’ OF CHEMOSENSATION —
UTILIZING CHEMOSENSORY SIGNALING
PATHWAYS OUTSIDE THE CANONICAL
CHEMOSENSORY ORGANS
Detection Of Irritants And Bacterial Metabolites Via
The Taste Transduction Cascade In Solitary Chemosensory
Cells Of The Nasal Cavity
Thomas Finger 1,3 , Sue Kinnamon 2,3 , Vijay Ramakrishnan 2 ,
Marco Tizzano 1,3
1
Dept. Cell & Devel. Biol., Univ Colo. Med. Sch. Aurora, CO, USA,
2
Dept. Otolaryngology, Univ Colo. Med. Sch. Aurora, CO, USA, 3 Rocky
Mountain Taste & Smell Center Aurora, CO, USA
Airways are continually assaulted by harmful compounds carried
on the incoming airstream and by the potentially pathogenic
bacterial populations. We have shown that the nasal epithelium
of rodents houses a population of trigeminally-innervated
solitary chemosensory cells (SCCs) that express T2R taste
receptors along with their downstream signaling components
crucial for detection and response to these deleterious agents.
SCCs are distributed across much of the nasal respiratory
epithelium in rodents, but are especially concentrated along
curved surfaces facing major airway conduits. In the upper
respiratory passageways, the SCCs express nearly all T2Rs tested
as well as some T1R family members. Downstream signaling
components also are expressed by SCCs including: gustducin,
PLCß2 and TrpM5. Functionally, SCCs respond rapidly to bitter
ligands (e.g. denatonium 10mM) as well as bacterial signaling
molecules including the acylhomoserine lactones produced as
quorum sensing molecules by Pseudomonas species. Activation
of the SCCs by these compounds evokes neurally-mediated
protective reflexes, involving both apnea and local neurogenic
inflammation. These responses are absent in both gustducin
and TrpM5 knockout mice implicating the taste transduction
cascade as a crucial component of responses to these substances.
Moreover, the local inflammatory responses were absent after
chemical ablation of the nociceptive fibers of the trigeminal
nerve showing the necessity for innervation. More recently we
have tested the possibility that similar SCCs are present in the
human nose and now report (S. Cooper AChemS 2013) the
presence of elongate TrpM5+ microvillous cells within the
sinonasal epithelium in humans. Whether similar SCCs underlie
epithelial defense systems in humans remains to be determined.
Acknowledgements: Supported by NIDCD grants to T. Finger,
SC Kinnamon (RO1 DC009820), M Tizzano (R03 DC012413)
and the Rocky Mountain Taste & Smell Center (P30 DC04657)
#59 SYMPOSIUM:
THE NEW ‘FACES’ OF CHEMOSENSATION —
UTILIZING CHEMOSENSORY SIGNALING
PATHWAYS OUTSIDE THE CANONICAL
CHEMOSENSORY ORGANS
Block of taste genes leads to male sterility
Bedrich Mosinger, Kevin M. Redding, Rockwell M. Parker,
Robert F. Margolskee
Monell Chemical Senses Center Philadelphia, PA, USA
The male infertility rate in the developing world is increasing.
About 7% of men are infertile for unknown reasons, while
having normal hormone levels. We found that two gene products
(T1R3 and gustducin) originally found in taste chemosensation
are expressed in haploid spermatids and their absence or
block leads to male sterility. The pathology shows an arrest in
spermatid development with numerous giant and exfoliated
cells in testicular tubules, oligospermia and immotile sperm.
To study this phenomenon we produced a mouse model
expressing a humanized form of T1R3 that can be inhibited
by human-specific inhibitors. Some of these inhibitors are
phenoxy compounds developed into common medications and
agricultural chemicals. A very effective, yet reversible, sterility
is achieved by treatment with the phenoxy compound clofibrate
in this model with humanized T1R3 receptor in the background
of gustducin null allele. Because both T1R3 and gustducin affect
cAMP levels, we hypothesize that their absence impairs function
of CREM (cAMP response modulator protein) a transcriptional
master gene indispensable for spermatid development and EPAC
(exchange protein activated by cAMP) a Rap 1 activator required
ORAL ABSTRACTS
Abstracts are printed as submitted by the author(s).
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