CGMP-dependent/independent

Gambaryan S, Geiger J, Schwarz UR, Butt E, Begonja A, Obergfell A, Walter U (2004) Potent inhibition of human platelets by cGMP analogs independent of cGMP-dependent protein kinase. Blood 103 2593-600... 

Phospholipids containing nnsaturated fatty acids can be nitrated to form nitro-fatty acids or nitroalkenes, as shown in Fignre 8.3 for PLPE. Nitroalkenes affect cell signaling in different ways, as shown for cGMP-dependent and -independent... 

MAHMA NONOate spontaneously dissociates in a pH-dependent, first-order process with a half-life of 1 min at 37 °C. In vivo, examination in anesthetised rats showed, that MAHMA NONOate had both platelet inhibitory and vasodepressor effects [50]. Like other NONOates, MAHMA NONOate inhibited collagen-induced and ADP-induced rat platelet aggregation in a concentration-dependent manner [51]. ODQ, a soluble GS inhibitor, caused only small influence on the concentration-response curve to MAHMA NONOate, indicating that cGMP-independent mechanisms play a crucial role. A potential target of MAHMA NONOate induced inhibition was the sarco-endoplasmic reticulum calcium-ATPase of the platelet dense tubular system... 

So far, there were no reports on endothelium-independent pephdes, except for camosine (P-Ala-His), by which cGMP produchon was shmu-lated in VSMC. As shown in Fig. 3, endothelium-independent or smooth muscle-dependent vasorelaxadon can be achieved by the suppression of... 

Furchgott, R.F., Jothianandin, S. (1991). Endothelium-dependent and -independent vasodilation involving cGMP relaxation induced by nitric oxide, carbon monoxide and light. Blood Vessels 28 52-61. 

PKG and PKA are serine/threonine kinases which become activated by agonists that evoke an increase in either cGMP levels or cAMP levels, respectively. Butt et al. (2000) recently reported that activation of PKG and PKA induced serine phosphorylation of eNOS rendering the enzyme Ca " -independent [39]. In this study eNOS was found to be phosphorylated on serine 1177, serine 633 and threonine 495 allowing for enzyme activation in the absence of calcium-calmodulin. Moreover as there are reports that PKA can activate Akt/PKB via a PI3-kinase dependent pathway [43], various intracellular kinase cascades may interact with one another leading to the control of eNOS activity via phosphorylation. 

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