# Effect of muscarinic receptor agonist on cilia sensory function and structure

> **NIH NIH R15** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 2020 · $34,212

## Abstract

Abstract:
Primary endothelial cilia are mechanosensory organelles that are projected into the lumen of blood vessels and
kidney tubules. Defects in cilia assembly or function can lead to multiple human pathologies, including
hypertension and Polycystic Kidney Disease (PKD). Acetylcholine, a neurotransmitter, is implicated in essential
hypertension in humans. It has been demonstrated that vascular endothelia require primary cilia to sense and
transmit external mechanical stimuli into internal biochemical reactions. One of these reactions includes the
biosynthesis and release of nitric oxide, which is one of the most potent endogenous vasodilators. Though both
primary cilia and muscarinic acetylcholine receptors play important roles in hypertension, their relationship has
never been explored. To determine the roles of the cholinergic system and mechanosensory cilia, we studied
the effects of acetylcholine receptor modulators on ciliary length and function in wild-type (WT) and mechano-
insensitive cilia mutant endothelial cells (Pkd1−/− and Tg737orpk/orpk). Studies from our lab showed for the first time
that mouse vascular endothelia exhibit muscarinic receptor-type 1, 3 and 5 (AChM1, 3, and 5R), which co-
localizes to primary endothelial cilia. AChM3R activation significantly increases cilia length in cells treated with
AChM3R agonist compared to non-treated cells. Furthermore, the chemosensory function of cilia can alter the
mechanosensory function through changes in sensitivity to fluid-shear stress. We propose that activated ciliary
AChM3R has a functional mechanosensory role in endothelial cells. This could enhance cilia sensory function
in response to NO production.

## Key facts

- **NIH application ID:** 10025768
- **Project number:** 3R15HL140523-01S2
- **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
- **Principal Investigator:** Wissam Aboualaiwi
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,212
- **Award type:** 3
- **Project period:** 2020-03-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025768

## Citation

> US National Institutes of Health, RePORTER application 10025768, Effect of muscarinic receptor agonist on cilia sensory function and structure (3R15HL140523-01S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10025768. Licensed CC0.

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