scholarly journals Stimulation of β-adrenoceptors inhibits store-operated channel currents via a cAMP-dependent protein kinase mechanism in rabbit portal vein myocytes

2005 ◽  
Vol 562 (2) ◽  
pp. 395-406 ◽  
Author(s):  
M Liu ◽  
WA Large ◽  
AP Albert
2008 ◽  
Vol 28 (11) ◽  
pp. 3804-3816 ◽  
Author(s):  
Rasmus Koefoed Petersen ◽  
Lise Madsen ◽  
Lone Møller Pedersen ◽  
Philip Hallenborg ◽  
Hanne Hagland ◽  
...  

ABSTRACT Cyclic AMP (cAMP)-dependent processes are pivotal during the early stages of adipocyte differentiation. We show that exchange protein directly activated by cAMP (Epac), which functions as a guanine nucleotide exchange factor for the Ras-like GTPases Rap1 and Rap2, was required for cAMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of cAMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response.


1999 ◽  
Vol 277 (5) ◽  
pp. G1048-G1054 ◽  
Author(s):  
Wei Qu ◽  
Lee M. Graves ◽  
Ronald G. Thurman

The aim of this study was to determine which PGE2 receptors and signal transduction pathways are responsible for the stimulation of oxygen uptake in liver. Hepatic parenchymal cells isolated from female Sprague-Dawley rats were incubated either with PGE2, 17-phenyl-omega-trinor PGE2 (an EP1-specific agonist), or 11-deoxy PGE1 (an EP2/EP4-specific agonist), and oxygen consumption was measured. Both PGE2 and 11-deoxy PGE1 stimulated oxygen consumption. However, an EP1agonist was without effect. Although PGE2 elevated intracellular calcium, this occurred at concentrations ∼500-fold lower than that required to stimulate oxygen uptake. PGE2-stimulated increases in cAMP formation correlated well with the increase in oxygen consumption. Dibutyryl cAMP also increased oxygen consumption. Furthermore, N-[2-( p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, a cell-permeable inhibitor of protein kinase A (PKA), reduced the stimulation of oxygen uptake by PGE2. Incubation of isolated parenchymal cell mitochondria with the purified catalytic subunit of PKA and ATP increased both state 3 rates of oxygen uptake and the respiratory control ratio by ∼50%. Activation of these events was prevented by incubation with the PKA inhibitory peptide, PKI. These findings are consistent with the hypothesis that PGE2 stimulates oxygen consumption via an EP2 and/or EP4 subclass of receptors through the actions of cAMP on a cAMP-dependent protein kinase.


1994 ◽  
Vol 64 ◽  
pp. 319
Author(s):  
F. Arakane ◽  
K. Fukunaga ◽  
K. Miyazaki ◽  
H. Okamura ◽  
E. Miyamoto

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