scholarly journals Stimulation of neuronal KATP channels by cGMP-dependent protein kinase: involvement of ROS and 5-hydroxydecanoate-sensitive factors in signal transduction

2010 ◽  
Vol 298 (4) ◽  
pp. C875-C892 ◽  
Author(s):  
Yongping Chai ◽  
Yu-Fung Lin
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Neuronal Excitability ◽  
Single Channel ◽  
Katp Channels ◽  
Membrane Excitability ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Stimulation Of

The ATP-sensitive potassium (KATP) channel couples intracellular metabolic state to membrane excitability. Recently, we demonstrated that neuronal KATP channels are functionally enhanced by activation of a nitric oxide (NO)/cGMP/cGMP-dependent protein kinase (PKG) signaling cascade. In this study, we further investigated the intracellular mechanism underlying PKG stimulation of neuronal KATP channels. By performing single-channel recordings in transfected HEK293 and neuroblastoma SH-SY5Y cells, we found that the increase of Kir6.2/SUR1 (i.e., the neuronal-type KATP) channel currents by PKG activation in cell-attached patches was diminished by 5-hydroxydecanoate (5-HD), an inhibitor of the putative mitochondrial KATP channel; N-(2-mercaptopropionyl)glycine, a reactive oxygen species (ROS) scavenger, and catalase, a hydrogen peroxide (H2O2)-decomposing enzyme. These reagents also ablated NO-induced KATP channel stimulation and prevented the shifts in the single-channel open- and closed-time distributions resulting from PKG activation and NO induction. Bath application of H2O2 reproduced PKG stimulation of Kir6.2/SUR1 but did not activate tetrameric Kir6.2LRKR368/369/370/371AAAA channels. Moreover, neither the PKG activator nor exogenous H2O2 was able to enhance the function of KATP channels in the presence of Ca2+ chelators and calmodulin antagonists, whereas the stimulatory effect of H2O2 was unaffected by 5-HD. Altogether, in this report we provide novel evidence that activation of PKG stimulates neuronal KATP channels by modulating intrinsic channel gating via a 5-HD-sensitive factor(s)/ROS/Ca2+/calmodulin signaling pathway that requires the presence of the SUR1 subunit. This signaling pathway may contribute to neuroprotection against ischemic injury and regulation of neuronal excitability and neurotransmitter release by modulating the function of neuronal KATP channels.

scholarly journals Inhibition of diuretic stimulation of an insect secretory epithelium by a cGMP-dependent protein kinase

2013 ◽  
Vol 304 (9) ◽  
pp. F1210-F1216 ◽  
Author(s):  
Kristen A. Ruka ◽  
Anna P. Miller ◽  
Edward M. Blumenthal
Keyword(s):  
Protein Kinase ◽  
Stellate Cells ◽  
Malpighian Tubules ◽  
Microelectrode Recording ◽  
Dependent Protein Kinase ◽  
Rnai Construct ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Diuretic Agents ◽  
Stimulation Of

The rate of urine secretion by insect Malpighian tubules (MTs) is regulated by multiple diuretic and antidiuretic hormones, often working either synergistically or antagonistically. In the Drosophila melanogaster MT, only diuretic factors have been reported. Two such agents are the biogenic amine tyramine (TA) and the peptide drosokinin (DK), both of which act on the stellate cells of the tubule to increase transepithelial chloride conductance. In the current study, TA and DK signaling was quantified by microelectrode recording of the transepithelial potential in isolated Drosophila MTs. Treatment of tubules with cGMP caused a significant reduction in the depolarizing responses to both TA and DK, while cAMP had no effect on these responses. To determine whether a specific cGMP-dependent protein kinase (PKG) was mediating this inhibition, PKG expression was knocked down by RNAi in either the principal cells or the stellate cells. Knockdown of Pkg21D in the stellate cells eliminated the modulation of TA and DK signaling. Knockdown of Pkg21D with a second RNAi construct also reduced the modulation of TA signaling. In contrast, knockdown of the expression of foraging or CG4839, which encodes a known and a putative PKG, respectively, had no effect. These data indicate that cGMP, acting through the Pkg21D gene product in the stellate cells, can inhibit signaling by the diuretic agents TA and DK. This represents a novel function for cGMP and PKG in the Drosophila MT and suggests the existence of an antidiuretic hormone in Drosophila .

scholarly journals Sequential activation of p38 and ERK pathways by cGMP-dependent protein kinase leading to activation of the platelet integrin αIIbβ3

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 965-972 ◽  
Author(s):  
Zhenyu Li ◽  
Guoying Zhang ◽  
Robert Feil ◽  
Jiahuai Han ◽  
Xiaoping Du
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Dominant Negative ◽  
Platelet Glycoprotein ◽  
Dominant Negative Mutant ◽  
Integrin Activation ◽  
Dependent Protein Kinase ◽  
Integrin Αiibβ3 ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein

AbstractIntegrin activation (inside-out signaling) in platelets can be initiated by agonists such as von Willebrand factor (VWF) and thrombin. Here we show that a mitogen-activated protein kinase (MAPK), p38, plays an important role in the activation of integrin αIIbβ3 induced by VWF and thrombin. A dominant-negative mutant of p38, p38AF, inhibits αIIbβ3 activation induced by VWF binding to its receptor, the platelet glycoprotein Ib-IX (GPIb-IX), and p38 inhibitors diminish platelet aggregation induced by VWF or low-dose thrombin. The inhibitory effect of p38 inhibitor is unlikely to be caused by the previous suggested effect on cyclo-oxygenase, as inhibition also was observed in the presence of high concentrations of cyclo-oxygenase inhibitor, aspirin. VWF or thrombin induces p38 activation, which is inhibited in cGMP-dependent protein kinase (PKG)-knockout mouse platelets and PKG inhibitor-treated human platelets, indicating that activation of p38 is downstream from PKG in the signaling pathway. p38AF or p38 inhibitors diminish PKG-induced phosphorylation of extracellular stimuli-responsive kinase (ERK), which also is important in integrin activation. Thus, p38 plays an important role in mediating PKG-dependent activation of ERK. These data delineate a novel signaling pathway in which platelet agonists sequentially activate PKG, p38, and ERK pathways leading to integrin activation.

Stimulation of cGMP-dependent protein kinase (G-kinase) by peptide-546

Neuropeptides ◽  
1994 ◽  
Vol 26 ◽  
pp. 3
Author(s):  
J.P. Huggins ◽  
A.J. Ganzhorn ◽  
V. Saudek ◽  
J.T. Pelton ◽  
R.A. Atkinson
Keyword(s):  
Protein Kinase ◽  
Protein Kinase G ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Stimulation Of
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