Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations

Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations

Termination of cyclic adenosine monophosphate (cAMP) signaling via the extracellular Ca2+-sensing receptor (CaR) was visualized in single CaR-expressing human embryonic kidney (HEK) 293 cells using ratiometric fluorescence resonance energy transfer–dependent cAMP sensors based on protein kinase A an...

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Main Authors: Gerbino, Andrea, Ruder, Warren C., Curci, Silvana, Pozzan, Tullio, Zaccolo, Manuela, Hofer, Aldebaran M.
Format: Online
Language:English
Published: The Rockefeller University Press 2005
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171199/
id pubmed-2171199
recordtype oai_dc
spelling pubmed-21711992008-03-05 Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations Gerbino, Andrea Ruder, Warren C. Curci, Silvana Pozzan, Tullio Zaccolo, Manuela Hofer, Aldebaran M. Research Articles Termination of cyclic adenosine monophosphate (cAMP) signaling via the extracellular Ca2+-sensing receptor (CaR) was visualized in single CaR-expressing human embryonic kidney (HEK) 293 cells using ratiometric fluorescence resonance energy transfer–dependent cAMP sensors based on protein kinase A and Epac. Stimulation of CaR rapidly reversed or prevented agonist-stimulated elevation of cAMP through a dual mechanism involving pertussis toxin–sensitive Gαi and the CaR-stimulated increase in intracellular [Ca2+]. In parallel measurements with fura-2, CaR activation elicited robust Ca2+ oscillations that increased in frequency in the presence of cAMP, eventually fusing into a sustained plateau. Considering the Ca2+ sensitivity of cAMP accumulation in these cells, lack of oscillations in [cAMP] during the initial phases of CaR stimulation was puzzling. Additional experiments showed that low-frequency, long-duration Ca2+ oscillations generated a dynamic staircase pattern in [cAMP], whereas higher frequency spiking had no effect. Our data suggest that the cAMP machinery in HEK cells acts as a low-pass filter disregarding the relatively rapid Ca2+ spiking stimulated by Ca2+-mobilizing agonists under physiological conditions. The Rockefeller University Press 2005-10-24 /pmc/articles/PMC2171199/ /pubmed/16247029 http://dx.doi.org/10.1083/jcb.200507054 Text en Copyright © 2005, 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/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Gerbino, Andrea
Ruder, Warren C.
Curci, Silvana
Pozzan, Tullio
Zaccolo, Manuela
Hofer, Aldebaran M.
spellingShingle Gerbino, Andrea
Ruder, Warren C.
Curci, Silvana
Pozzan, Tullio
Zaccolo, Manuela
Hofer, Aldebaran M.
Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations
author_facet Gerbino, Andrea
Ruder, Warren C.
Curci, Silvana
Pozzan, Tullio
Zaccolo, Manuela
Hofer, Aldebaran M.
author_sort Gerbino, Andrea
title Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations
title_short Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations
title_full Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations
title_fullStr Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations
title_full_unstemmed Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations
title_sort termination of camp signals by ca2+ and gαi via extracellular ca2+ sensors: a link to intracellular ca2+ oscillations
description Termination of cyclic adenosine monophosphate (cAMP) signaling via the extracellular Ca2+-sensing receptor (CaR) was visualized in single CaR-expressing human embryonic kidney (HEK) 293 cells using ratiometric fluorescence resonance energy transfer–dependent cAMP sensors based on protein kinase A and Epac. Stimulation of CaR rapidly reversed or prevented agonist-stimulated elevation of cAMP through a dual mechanism involving pertussis toxin–sensitive Gαi and the CaR-stimulated increase in intracellular [Ca2+]. In parallel measurements with fura-2, CaR activation elicited robust Ca2+ oscillations that increased in frequency in the presence of cAMP, eventually fusing into a sustained plateau. Considering the Ca2+ sensitivity of cAMP accumulation in these cells, lack of oscillations in [cAMP] during the initial phases of CaR stimulation was puzzling. Additional experiments showed that low-frequency, long-duration Ca2+ oscillations generated a dynamic staircase pattern in [cAMP], whereas higher frequency spiking had no effect. Our data suggest that the cAMP machinery in HEK cells acts as a low-pass filter disregarding the relatively rapid Ca2+ spiking stimulated by Ca2+-mobilizing agonists under physiological conditions.
publisher The Rockefeller University Press
publishDate 2005
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171199/
_version_ 1611424543801344000

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