Calmodulin Regulates Ciliary Beats in the Human Nasal Mucosa Through Adenylate/Guanylate Cyclases and Protein Kinases A/G
Autor: | Thi Nga Nguyen, Jun-ichi Ohkubo, Takuro Kitamura, Hideaki Suzuki, Tetsuro Wakasugi |
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Rok vydání: | 2021 |
Předmět: |
Calmodulin
Immunology Adenylate kinase chemistry.chemical_compound Cyclic GMP-Dependent Protein Kinases Humans Immunology and Allergy Cilia Sinusitis Cyclic GMP Rhinitis Forskolin biology Activator (genetics) Kinase Endoscopy General Medicine KT5720 Cyclic AMP-Dependent Protein Kinases Protein Kinase A Inhibitor Cell biology Nasal Mucosa chemistry Guanylate Cyclase Mucociliary Clearance biology.protein Calcium cGMP-dependent protein kinase Adenylyl Cyclases Signal Transduction |
Zdroj: | International Archives of Allergy and Immunology. 182:800-806 |
ISSN: | 1423-0097 1018-2438 |
Popis: | Background: The ciliary beat of the airway epithelium, including the sinonasal epithelium, has a significant role in frontline defense and is thought to be controlled by the level of intracellular Ca2+. Involvement of calmodulin and adenylate/guanylate cyclases in the regulation of ciliary beats has been reported, and here we investigated the interrelation between these components of the ciliary beat regulatory pathway. Methods: The inferior turbinates were collected from 29 patients with chronic hypertrophic rhinitis/rhinosinusitis during endoscopic sinonasal surgery. The turbinate mucosa was cut into thin strips, and mucociliary movement was observed under a phase-contrast light microscope equipped with a high-speed digital video camera. Results: The ciliary beat frequency (CBF) was significantly increased by stimulation with 100 μM CALP3 (calmodulin agonist), which was completely suppressed by adding 100 µM SQ22536 (adenylate cyclase inhibitor) and 10 µM ODQ (guanylate cyclase inhibitor) together and by adding 1 µM KT5720 (protein kinase A inhibitor) and 1 µM KT5823 (protein kinase G inhibitor) together. The CBF was significantly increased by stimulation with 10 µM forskolin (adenylate cyclase activator) and 10 µM BAY41-2272 (guanylate cyclase activator) and by stimulation with 100 µM 8-bromo-cAMP (cAMP analog) and 100 µM 8-bromo-cGMP (cGMP analog), which was not changed by adding 1 µM calmidazolium (calmodulin antagonist). Conclusions: These results confirmed that the regulatory pathway of ciliary beats in the human nasal mucosa involves calmodulin, adenylate/guanylate cyclases, and protein kinases A/G and indicate that adenylate/guanylate cyclases and protein kinases A/G act downstream of calmodulin, but not vice versa, and that these cyclases relay calmodulin signaling. |
Databáze: | OpenAIRE |
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