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The Mechanism of Ciliary Stimulation by Acetylcholine: Roles of Calcium, PKA, and PKG
Stimulation of ciliary cells through muscarinic receptors leads to a strong biphasic enhancement of ciliary beat frequency (CBF). The main goal of this work is to delineate the chain of molecular events that lead to the enhancement of CBF induced by acetylcholine (ACh). Here we show that the Ca(2+),...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2311390/ https://www.ncbi.nlm.nih.gov/pubmed/11929884 http://dx.doi.org/10.1085/jgp.20028519 |
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author | Zagoory, Orna Braiman, Alex Priel, Zvi |
author_facet | Zagoory, Orna Braiman, Alex Priel, Zvi |
author_sort | Zagoory, Orna |
collection | PubMed |
description | Stimulation of ciliary cells through muscarinic receptors leads to a strong biphasic enhancement of ciliary beat frequency (CBF). The main goal of this work is to delineate the chain of molecular events that lead to the enhancement of CBF induced by acetylcholine (ACh). Here we show that the Ca(2+), cGMP, and cAMP signaling pathways are intimately interconnected in the process of cholinergic ciliary stimulation. ACh induces profound time-dependent increase in cGMP and cAMP concentrations mediated by the calcium–calmodulin complex. The initial strong CBF enhancement in response to ACh is mainly governed by PKG and elevated calcium. The second phase of CBF enhancement induced by ACh, a stable moderately elevated CBF, is mainly regulated by PKA in a Ca(2+)-independent manner. Inhibition of either guanylate cyclase or of PKG partially attenuates the response to ACh of [Ca(2+)](i), but completely abolishes the response of CBF. Inhibition of PKA moderately attenuates and significantly shortens the responses to ACh of both [Ca(2+)](i) and CBF. In addition, PKA facilitates the elevation in [Ca(2+)](i) and cGMP levels induced by ACh, whereas an unimpeded PKG activity is essential for CBF enhancement mediated by either Ca(2+) or PKA. |
format | Text |
id | pubmed-2311390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-23113902008-04-21 The Mechanism of Ciliary Stimulation by Acetylcholine: Roles of Calcium, PKA, and PKG Zagoory, Orna Braiman, Alex Priel, Zvi J Gen Physiol Article Stimulation of ciliary cells through muscarinic receptors leads to a strong biphasic enhancement of ciliary beat frequency (CBF). The main goal of this work is to delineate the chain of molecular events that lead to the enhancement of CBF induced by acetylcholine (ACh). Here we show that the Ca(2+), cGMP, and cAMP signaling pathways are intimately interconnected in the process of cholinergic ciliary stimulation. ACh induces profound time-dependent increase in cGMP and cAMP concentrations mediated by the calcium–calmodulin complex. The initial strong CBF enhancement in response to ACh is mainly governed by PKG and elevated calcium. The second phase of CBF enhancement induced by ACh, a stable moderately elevated CBF, is mainly regulated by PKA in a Ca(2+)-independent manner. Inhibition of either guanylate cyclase or of PKG partially attenuates the response to ACh of [Ca(2+)](i), but completely abolishes the response of CBF. Inhibition of PKA moderately attenuates and significantly shortens the responses to ACh of both [Ca(2+)](i) and CBF. In addition, PKA facilitates the elevation in [Ca(2+)](i) and cGMP levels induced by ACh, whereas an unimpeded PKG activity is essential for CBF enhancement mediated by either Ca(2+) or PKA. The Rockefeller University Press 2002-04 /pmc/articles/PMC2311390/ /pubmed/11929884 http://dx.doi.org/10.1085/jgp.20028519 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Zagoory, Orna Braiman, Alex Priel, Zvi The Mechanism of Ciliary Stimulation by Acetylcholine: Roles of Calcium, PKA, and PKG |
title | The Mechanism of Ciliary Stimulation by Acetylcholine: Roles of Calcium, PKA, and PKG |
title_full | The Mechanism of Ciliary Stimulation by Acetylcholine: Roles of Calcium, PKA, and PKG |
title_fullStr | The Mechanism of Ciliary Stimulation by Acetylcholine: Roles of Calcium, PKA, and PKG |
title_full_unstemmed | The Mechanism of Ciliary Stimulation by Acetylcholine: Roles of Calcium, PKA, and PKG |
title_short | The Mechanism of Ciliary Stimulation by Acetylcholine: Roles of Calcium, PKA, and PKG |
title_sort | mechanism of ciliary stimulation by acetylcholine: roles of calcium, pka, and pkg |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2311390/ https://www.ncbi.nlm.nih.gov/pubmed/11929884 http://dx.doi.org/10.1085/jgp.20028519 |
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