Calmodulin Regulates Ciliary Beats in the Human Nasal Mucosa Through Adenylate/Guanylate Cyclases and Protein Kinases A/G

2021 ◽  
pp. 1-7
Author(s):  
Thi Nga Nguyen ◽  
Hideaki Suzuki ◽  
Jun-ichi Ohkubo ◽  
Tetsuro Wakasugi ◽  
Takuro Kitamura
Keyword(s):  
Protein Kinase ◽  
Adenylate Cyclase ◽  
Protein Kinases ◽  
Nasal Mucosa ◽  
Guanylate Cyclase ◽  
Regulatory Pathway ◽  
Calmodulin Antagonist ◽  
Human Nasal Mucosa ◽  
Cyclase Activator ◽  
Ciliary Beat

<b><i>Background:</i></b> 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 Ca<sup>2+</sup>. 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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). <b><i>Conclusions:</i></b> 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.

Correlation Between Ciliary Beat Frequency and the Structure of Ciliated Epithelia in Pathologic Human Nasal Mucosa

1998 ◽  
Vol 108 (3) ◽  
pp. 426-430 ◽  
Author(s):  
Susanna Joki ◽  
Elina Toskala ◽  
Veijo Saano ◽  
Juhani Nuutinen
Keyword(s):  
Nasal Mucosa ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Human Nasal Mucosa ◽  
Ciliary Beat

Acetylcholine-induced Ciliary Beat of the Human Nasal Mucosa Is Regulated by the Pannexin-1 Channel and Purinergic P2X Receptor

2018 ◽  
Vol 32 (4) ◽  
pp. 217-227 ◽  
Author(s):  
Ba H. Do ◽  
Toyoaki Ohbuchi ◽  
Tetsuro Wakasugi ◽  
Hiroki Koizumi ◽  
Mitsuru Yokoyama ◽  
...  
Keyword(s):  
Nasal Mucosa ◽  
Intracellular Signaling ◽  
Regulatory Mechanism ◽  
Beat Frequency ◽  
P2x Receptor ◽  
Flufenamic Acid ◽  
Disulfonic Acid ◽  
Human Nasal Mucosa ◽  
Pannexin 1 ◽  
Ciliary Beat

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 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, 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.

scholarly journals Novel Protein Kinase Induced during Sporangial Cleavage in the Oomycete Phytophthora infestans

2002 ◽  
Vol 1 (5) ◽  
pp. 687-695 ◽  
Author(s):  
Howard S. Judelson ◽  
Samuel Roberts
Keyword(s):  
Protein Kinase ◽  
Phytophthora Infestans ◽  
Protein Kinases ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Protein Kinase Inhibitors ◽  
Kinase Gene ◽  
Mrna Accumulation ◽  
Calmodulin Antagonist ◽  
Zoospore Release

ABSTRACT A study of the effect of inhibitors on zoospore development in Phytophthora infestans demonstrated the involvement of protein kinases and calcium and led to the discovery of a gene induced during zoosporogenesis that encoded a protein resembling Ca+2- and calmodulin-regulated serine/threonine protein kinases. The calcium channel blocker verapamil and the calmodulin antagonist trifluoroperazine inhibited zoosporogenesis and encystment. The protein kinase inhibitors K-252a and KN-93 inhibited zoospore release, encystment, and cyst germination, and K-252a reduced zoospore viability. In contrast, the inhibitors had minor or no effects on sporangia directly germinating in media. Spurred by these findings, a survey of putative protein kinase genes was performed to identify any that were up-regulated during zoosporogenesis. A kinase-encoding gene was identified for which mRNA accumulation was first detected soon after chilling sporangia in water, conditions that induce sporangial cytoplasm to cleave and release zoospores. The transcript persisted in motile zoospores and in germinated cysts but was not detected in other tissues, including hyphae, hyphae placed in water, or directly germinating sporangia. The structure of the predicted protein was novel, as its C-terminal region, which binds calmodulin in related proteins, was unusually short. Concentrations of actinomycin D previously used in experiments that suggested that de novo transcription was not needed for zoosporogenesis or encystment only partially inhibited transcription of the kinase gene, probably due to poor uptake into sporangia.

Influence of topical antifungal drugs on ciliary beat frequency of human nasal mucosa

2010 ◽  
Vol 120 (7) ◽  
pp. 1444-1448 ◽  
Author(s):  
Thiemo Hofmann ◽  
Sabine Reinisch ◽  
Claus Gerstenberger ◽  
Wolfgang Koele ◽  
Markus Gugatschka ◽  
...  
Keyword(s):  
Nasal Mucosa ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Antifungal Drugs ◽  
Human Nasal Mucosa ◽  
Ciliary Beat

Toxic Rhinitis-Induced Changes of Human Nasal Mucosa Innervation

2003 ◽  
Vol 31 (3) ◽  
pp. 326-331 ◽  
Author(s):  
David A. Groneberg ◽  
Werner Heppt ◽  
Annette Cryer ◽  
Anke Wussow ◽  
Christian Peiser ◽  
...  
Keyword(s):  
Nasal Mucosa ◽  
Human Nasal Mucosa ◽  
Induced Changes
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