Soluble guanylate cyclase activation synthesis

Rodent KC and HC, as well as human HC, express an inducible NO synthase under septic or inflammatory conditions. In vivo in endotoxemia, this expression is transient. Our in vivo data indicate that this induced -NO serves a protective role in the liver and reduces hepatic injury in endotoxemia. This protective action may be mediated by the capacity of NO to neutralize oxygen radicals and prevent platelet adherence and aggregation. Our in vitro studies show that HC-derived -NO can activate soluble guanylate cyclase. Other in vitro effects include the nonspecific suppression of protein synthesis and a small reduction in mitochondrial aconitase activity. The relevance of these in vitro actions to hepatic function in vivo remains to be determined. 

Soluble guanylate cyclase is activated by nitric oxide (NO) (see Section 3.4). NO has been implicated in the generation of long term depression (LTD) of parallel fiber-mediated EPSP s in Purkinje cells. LTD can be prevented by the application of haemoglobin that absorbs NO, or by the inhibition of NO synthesis (Crepel and Jaillard, 1990 Shibuki and Okada, 1991 Ito, 1991). However, nitric oxide synthase, the synthesizing enzyme of NO, appears to be absent from the Purkinje cell (Section 3.4.). 

Following its synthesis NO, both in endothelial cells and in the adjacent smooth muscle cells, activates what has been termed its intracellular receptor, soluble guanylate cyclase. NO binds to the heme iron in the catalytic domain of the enzyme and by increasing its activity leads to an enhanced formation of cGMP (Drexler et al., 1989 Martin et al.,... 

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