scholarly journals Epac1 mediates Protein Kinase A (PKA) independent mechanism of forskolin (FSK) stimulated Cl secretion in T84 cells

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Mirajul Hoque Kazi ◽  
Damian B Rossum ◽  
Linxi Chen ◽  
Chung‐Ming Tse
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
T84 Cells ◽  
Cl Secretion ◽  
Independent Mechanism ◽  
Kinase A

scholarly journals Epac1 mediates protein kinase A–independent mechanism of forskolin-activated intestinal chloride secretion

2009 ◽  
Vol 135 (1) ◽  
pp. 43-58 ◽  
Author(s):  
Kazi Mirajul Hoque ◽  
Owen M. Woodward ◽  
Damian B. van Rossum ◽  
Nicholas C. Zachos ◽  
Linxi Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Chinese Hamster Ovary Cells ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Chinese Hamster ◽  
T84 Cells ◽  
Cl Secretion ◽  
Intestinal Chloride Secretion ◽  
Kinase A

Intestinal Cl− secretion is stimulated by cyclic AMP (cAMP) and intracellular calcium ([Ca2+]i). Recent studies show that protein kinase A (PKA) and the exchange protein directly activated by cAMP (Epac) are downstream targets of cAMP. Therefore, we tested whether both PKA and Epac are involved in forskolin (FSK)/cAMP-stimulated Cl− secretion. Human intestinal T84 cells and mouse small intestine were used for short circuit current (Isc) measurement in response to agonist-stimulated Cl− secretion. FSK-stimulated Cl− secretion was completely inhibited by the additive effects of the PKA inhibitor, H89 (1 µM), and the [Ca2+]i chelator, 1,2-bis-(o-aminophenoxy)-ethane-N,N,N’,N’-tetraacetic acid, tetraacetoxymethyl ester (BAPTA-AM; 25 µM). Both FSK and the Epac activator 8-pCPT-2’-O-Me-cAMP (50 µM) elevated [Ca2+]i, activated Ras-related protein 2, and induced Cl− secretion in intact or basolateral membrane–permeabilized T84 cells and mouse ileal sheets. The effects of 8-pCPT-2’-O-Me-cAMP were completely abolished by BAPTA-AM, but not by H89. In contrast, T84 cells with silenced Epac1 had a reduced Isc response to FSK, and this response was completely inhibited by H89, but not by the phospholipase C inhibitor U73122 or BAPTA-AM. The stimulatory effect of 8-pCPT-2’-O-Me-cAMP on Cl− secretion was not abolished by cystic fibrosis transmembrane conductance (CFTR) inhibitor 172 or glibenclamide, suggesting that CFTR channels are not involved. This was confirmed by lack of effect of 8-pCPT-2’-O-Me-cAMP on whole cell patch clamp recordings of CFTR currents in Chinese hamster ovary cells transiently expressing the human CFTR channel. Furthermore, biophysical characterization of the Epac1-dependent Cl− conductance of T84 cells mounted in Ussing chambers suggested that this conductance was hyperpolarization activated, inwardly rectifying, and displayed a Cl−>Br−>I− permeability sequence. These results led us to conclude that the Epac-Rap-PLC-[Ca2+]i signaling pathway is involved in cAMP-stimulated Cl− secretion, which is carried by a novel, previously undescribed Cl− channel.

Protein Kinase A-Independent Mechanism of cAMP in Insulin Secretion

2008 ◽  
pp. 133-146
Author(s):  
Susumu Seino ◽  
Takashi Miki ◽  
Tadao Shibasaki
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Independent Mechanism ◽  
Kinase A

scholarly journals N6-Substituted cAMP Analogs Inhibit bTREK-1 K+ Channels and Stimulate Cortisol Secretion by a Protein Kinase A-Independent Mechanism

2009 ◽  
Vol 76 (6) ◽  
pp. 1290-1301 ◽  
Author(s):  
Haiyan Liu ◽  
Judith A. Enyeart ◽  
John J. Enyeart
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cortisol Secretion ◽  
K Channels ◽  
Independent Mechanism ◽  
Kinase A

scholarly journals Epac1 mediates protein kinase A–independent mechanism of forskolin-activated intestinal chloride secretion

2009 ◽  
Vol 187 (7) ◽  
pp. i18-i18
Author(s):  
Kazi Mirajul Hoque ◽  
Owen M. Woodward ◽  
Damian B. van Rossum ◽  
Nicholas C. Zachos ◽  
Linxi Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Chloride Secretion ◽  
Independent Mechanism ◽  
Intestinal Chloride Secretion ◽  
Kinase A

scholarly journals Prostaglandin E 2 ‐Stimulated Cl − Secretion in Airway Epithelium Involves Protein Kinase A and Calcium Crosstalk

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Shayda Abazari ◽  
Gopika Hari ◽  
Elizabeth Crowther ◽  
Franny Kiles ◽  
Annie Trumbull ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Airway Epithelium ◽  
Prostaglandin E ◽  
Cl Secretion ◽  
Kinase A

HA1004, an inhibitor of serine/threonine protein kinases, restores the sensitivity of thymic lymphomas to Ca2+-mediated apoptosis through a protein kinase A-independent mechanism

2002 ◽  
Vol 2 (4) ◽  
pp. 435-442 ◽  
Author(s):  
Janusz Matuszyk ◽  
Malgorzata Cebrat ◽  
Wojciech Kalas ◽  
Leon Strzadala
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Kinases ◽  
Independent Mechanism ◽  
Kinase A

scholarly journals Sphingosine Activates Protein Kinase A Type II by a Novel cAMP-independent Mechanism

2005 ◽  
Vol 280 (28) ◽  
pp. 26011-26017 ◽  
Author(s):  
Yuefang Ma ◽  
Stuart Pitson ◽  
Timothy Hercus ◽  
Jane Murphy ◽  
Angel Lopez ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Type Ii ◽  
Independent Mechanism ◽  
Kinase A

Elastin Peptides Activate Extracellular Signal-Regulated Kinase 1/2 via a Ras-Independent Mechanism Requiring Both p110γ/Raf-1 and Protein Kinase A/B-Raf Signaling in Human Skin Fibroblasts

2005 ◽  
Vol 67 (4) ◽  
pp. 1315-1324 ◽  
Author(s):  
Laurent Duca ◽  
Elise Lambert ◽  
Romain Debret ◽  
Bernard Rothhut ◽  
Charlotte Blanchevoye ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Human Skin ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Independent Mechanism ◽  
Kinase A

scholarly journals αMSH and Cyclic AMP Elevating Agents Control Melanosome pH through a Protein Kinase A-independent Mechanism

2009 ◽  
Vol 284 (28) ◽  
pp. 18699-18706 ◽  
Author(s):  
Yann Cheli ◽  
Flavie Luciani ◽  
Mehdi Khaled ◽  
Laurent Beuret ◽  
Karine Bille ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Independent Mechanism ◽  
Kinase A
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