# Bitter and sweet taste receptor physiology in airway ciliated cells

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $46,930

## Abstract

PROJECT SUMMARY
 T2R bitter taste receptors in airway cell cilia detect bacterial acyl-homoserine lactones
and quinolones. Activation of these T2Rs increases nitric oxide (NO) production to increase
ciliary beating and kill bacteria. T2Rs thus play an important role in airway innate immunity.
Polymorphisms that reduce the function of cilia T2Rs correlate with increased gram negative
upper respiratory infections, susceptibility to chronic rhinosinusitis, and worse surgical outcomes
after sinus surgery. Targeting T2Rs or enhancing their activity may be a complementary or
alternative to antibiotics. Boosting endogenous T2R-mediated immunity in the airway or other
organs may be a useful anti-pathogen strategy in the face of the increasing prevalence of
antibiotic-resistant “superbugs.” NO can be bactericidal and also can inactivate viruses.
 T2Rs also activate NO production in other tissues and immune cells like macrophages,
where T2R to NO signaling regulates phagocytosis. T2Rs activate the endothelial (e) form of
nitric oxide synthase (eNOS) in both primary airway cells and macrophages. This pathway
appears to be a hallmark of T2R signaling in many cell types and regulates multiple
physiological processes. Understanding how T2Rs signal to eNOS is critical for understanding
extraoral taste receptor signaling in many tissues. We hypothesize that T2R to eNOS signaling
requires phosphorylation of eNOS by kinases activated downstream of the T2Rs. Kinase
pathways activated by T2Rs are very unexplored compared with many other GPCRs. We also
hypothesize that this kinase phosphorylation is enhanced by HSP90, an important cellular
chaperone protein involved in NOS function as well as some GPCR signaling.
 In this proposal, we will investigate T2R-mediated phosphorylation of NOS and
consequences for NO production in primary nasal epithelial cells isolated from residual surgical
material and grown at air-liquid interface (Aim 1). We will use live cell imaging of NO production
and biochemistry combined with well-characterized pharmacological inhibitors of kinase
pathways known to activate eNOS. We will also use well characterized pharmacological HSP90
inhibitors to characterize if HSP90 regulates T2R or eNOS localization to airway cilia or function
(calcium signaling or NO production).

## Key facts

- **NIH application ID:** 10440041
- **Project number:** 3R01DC016309-04S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Robert J. Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,930
- **Award type:** 3
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440041

## Citation

> US National Institutes of Health, RePORTER application 10440041, Bitter and sweet taste receptor physiology in airway ciliated cells (3R01DC016309-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10440041. Licensed CC0.

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