Acetylcholine-induced Ciliary Beat of the Human Nasal Mucosa Is Regulated by the Pannexin-1 Channel and Purinergic P2X Receptor
| Autor: | Ba H Do, Toyoaki Ohbuchi, Nobusuke Hohchi, Hideaki Suzuki, Tetsuro Wakasugi, Hiroki Koizumi, Mitsuru Yokoyama |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Adolescent Connexin Mucous membrane of nose Nerve Tissue Proteins Turbinates Connexins 03 medical and health sciences Young Adult 0302 clinical medicine Immunology and Allergy Medicine Humans Inositol 1 4 5-Trisphosphate Receptors Cilia 030223 otorhinolaryngology Ciliary beating Receptor Cells Cultured Aged Rhinitis Aged 80 and over business.industry Purinergic receptor General Medicine Pannexin Middle Aged Acetylcholine Cell biology Nasal Mucosa 030104 developmental biology medicine.anatomical_structure Otorhinolaryngology Mucociliary Clearance Receptors Purinergic P2X Chronic Disease Carbenoxolone Female business medicine.drug Respiratory tract Signal Transduction |
| Zdroj: | American journal of rhinologyallergy. 32(4) |
| ISSN: | 1945-8932 |
| Popis: | BackgroundAirway 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.MethodsThe 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.ResultsCilia 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 Ca2+. 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. Conclusions: These results indicate that the regulatory mechanism of the Ach-induced ciliary beat is dependent on extracellular Ca2+and involves the muscarinic Ach receptor, IP3receptor, 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. |
| Databáze: | OpenAIRE |
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