# Role of P2Y2 in the Regulation of Vascular Tone and Control of Breathing

> **NIH NIH F31** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $40,211

## Abstract

PROJECT SUMMARY/ABSTRACT
Chemoreception is the mechanism by which the brain regulates breathing in response to changes in tissue
CO2/H+. This process is critical for maintaining brain CO2/H+ levels within the narrow range that is conducive for
normal neural function. Chemosensitive neurons in the Retrotrapezoid Nucleus (RTN) are directly responsible
for increasing respiratory activity and send excitatory projections to respiratory rhythm generating centers in
response to CO2/H+. Chemosensitive astrocytes in the RTN release ATP in response to CO2/H+ that directly
gains up neuronal activation to modulate respiratory activity and indirectly constrict RTN arterioles by activation
of P2Y2/4 receptors. Arteriole vasoconstriction prevents stimulus washout which gains up neuronal and astrocytic
responses to CO2/H+. An unexplored area of brainstem chemoreceptor research is the role heterogenetic
vasculature in supporting regional functionality. The long-term goal for this fellowship will be to molecularly
characterize heterogenetic arteriole cell types in brainstem chemosensing regions and non-chemosensitive
areas to provide potential targets for therapeutic action in breathing related disorders. This will be achieved by
using cell isolation methods in transgenic fluorescent mouse models for isolation of both endothelial cells and
vascular smooth muscle cells. Subsequent FACS and purinergic receptor expression profiling using qPCR will
demonstrate the unique properties of arterioles in different brain regions, as previously seen in vitro. By using
transgenic knock out mouse models, specific purinergic receptors on arteriole cell types can profiled for
functionality and importance for a normal breathing phenotype. This will be accomplished with selective
purinergic receptor isoform knock out mouse models using both in vivo and in vitro studies. In vitro arteriole slice
recordings compare and contrast arteriole behavior. Whole animal plethysmography and viral knockdown
models confirm in vitro arteriole recordings as well as provide evidence on the impact of vasculature dysfunction
in whole animal breathing physiology. These results can be utilized further by other researchers in the field for
more in-depth investigation of heterogenetic vasculature in other areas of the brain and body as well as provide
molecular targets to potentially remediate breathing phenotypes in disease states.

## Key facts

- **NIH application ID:** 9925096
- **Project number:** 5F31HL142227-03
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Colin Cleary
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,211
- **Award type:** 5
- **Project period:** 2018-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925096

## Citation

> US National Institutes of Health, RePORTER application 9925096, Role of P2Y2 in the Regulation of Vascular Tone and Control of Breathing (5F31HL142227-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9925096. Licensed CC0.

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