Acetylcholine-induced Ciliary Beat of the Human Nasal Mucosa Is Regulated by the Pannexin-1 Channel and Purinergic P2X Receptor. Issue 4 (July 2018)

• Record Type: Journal Article
• Authors: Do, Ba H.; Ohbuchi, Toyoaki; Wakasugi, Tetsuro; Koizumi, Hiroki; Yokoyama, Mitsuru; Hohchi, Nobusuke; Suzuki, Hideaki
• Is Part Of: American journal of rhinology & allergy. Volume 32:Issue 4(2018)
• Page Start: 217
• Page End: 227
• Publication Date: 2018-07
• Subjects: human nasal mucosa -- inferior turbinate -- mucociliary transport -- ciliary beat frequency -- ATP -- acetylcholine -- pannexin-1 -- P2X receptor -- connexin; Nose -- Periodicals; Allergy -- Periodicals; 616.21005
• DOI: 10.1177/1945892418770292
• Languages: English
• ISSNs: 1945-8924

Abstract

Background: Airway mucociliary transport is an important function for the clearance of inhaled foreign particulates in the respiratory tract. The present study aimed at investigating the regulatory mechanism of acetylcholine (Ach)-induced ciliary beat of the human nasal mucosa in ex vivo . Methods: The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic surgery. The mucosa was cut into thin strips, and ciliary movement was observed under a phase-contrast light microscope with a high-speed digital video camera. The sample was alternatively subjected to scanning electron microscopic observation. Results: Cilia on the turbinate epithelium were well preserved at the ultrastructural level. The baseline ciliary beat frequency (CBF) was 6.45 ± 0.32 Hz. CBF was significantly increased by stimulation with 100 µM Ach and 100 µM adenosine triphosphate. The Ach-induced CBF increase was completely inhibited by removing extracellular Ca 2+ . Significant inhibition of the Ach-induced CBF was also observed by the addition of 1 µM atropine, 40 µM 2-aminoethoxydiphenyl borate (inositol trisphosphate [IP3 ] receptor antagonist), 10 µM carbenoxolone (pannexin-1 blocker), 1 mM probenecid (pannexin-1 blocker), 100 µM pyridoxalphosphate-6-azophenyl-20, 40-disulfonic acid (P2X antagonist), and 300 µM flufenamic acid (connexin blocker). Meanwhile, 30 nM bafilomycin A1 (vesicular transport inhibitor) did not inhibit the Ach-induced CBF increase. Conclusion s: These results indicate that the regulatory mechanism of the Ach-induced ciliary beat is dependent on extracellular Ca 2+ and involves the muscarinic Ach receptor, IP3 receptor, pannexin-1 channel, purinergic P2X receptor, and connexin channel. We proposed a tentative intracellular signaling pathway of the Ach-induced ciliary beat, in which the pannexin-1-P2X unit may play a central role in ciliary beat regulation.