Guanyl soluble

Lydic, R., Garza-Grande, R., Struthers, R. Baghdoyan, H. A. (2006). Nitric oxide in B6 mouse and nitric oxide-sensitive soluble guanylate cyclase in cat modulate acetylcholine release in pontine reticular formation. J. Appl. Physiol 100, 1666-73. 

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

In vitro activation of soluble guanyl cyclase and nitric oxide release a comparison of NO donors and NO mimetics Biochemistry 40 (2001),... 

Dimethyl-l,2,5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide (41) is also an old product [7,11, 31] that has recently been found to react with GSH to give S-nitrosogluta-thione, NO and HNO [32]. It stimulates partially purified rat lung soluble guanylate cyclase, but not the heme-deficient enzyme. The activation is inhibited by ODQ. The product also displays significant vasodilator activity on rat thoracic aorta rings at nanomolar concentrations. Finally, [l,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide derivatives (42, R,Ri=CH3,H) release NO, detected as nitrite, in the presence of thiols. A mechanism for this release has been proposed [33]. 

Mesoionic oxatriazolium-5-amenates 83 exhibit the whole range of biological properties typical of NO-releasing compounds that stimulate soluble guanylate cyclase namely antihypertensive activity in animals following the relaxation of the vascular... 

In its raw form, exogenous NO donation as pure NO gas must be considered as a possible therapeutic route. Unlike all previous subdivisions, administration of this kind is obviously independent of any chemical or enzymatic process prior to the activation of soluble guanylate cyclase. This route lacks sophistication, and can... 

DETA/NO is a stable NO-donor with the longest NO generation half-life of approximately 20 h. Thrombelastography performed on rabbit blood showed that DETA NONOate-derived NO significantly decreased coagulation activity and platelet activation [48]. Monitoring by intravital microscopy showed that DETA/NO attenuated the platelets/endothelial cells adhesion response to endotoxins (e.g. lipopolysaccharides) in murine intestinal venules [49]. The main mechanism of the antiadhesive action of DETA/NO on platelets was activation of soluble guanylate cyclase [49]. 

Nitric oxide (NO) is synthesized by vascular endothelium in response to vasodilators. It diffuses into the surrounding vascular smooth muscle, where it directly binds the heme group of soluble guanylate cyclase, activating the enzyme. 

Both the ANF receptor and the soluble guanylate cydase are assodated with the same vascular smooth musde cells. These cGMP systems are shown in Figure 1-9-3. 

Nitric oxide diffuses into the cell and directly activates a soluble, cytoplasmic guanylate cyclase, so no receptor or G protein is required. 

E. activate a soluble guanyl cyclase enzyme in vascular smooth musde... 

Effect Activates soluble guanylate Activates soluble guanylate... 

Fig. 1. Nitric oxide (NO) synthesis by nitric oxide synthase (NOS) (upper left), NO reaction with soluble guanylate cyclase (sGC) (middle), and formation of cyclic GMP, which causes tissue-specific signaling (right). The roles of the salivary nitrophorins from Rhodnius prolixus in storing and releasing NO and binding histamine are included (lower left).

Guanylate cyclase catalyzes the conversion of GTP to cGMP and exists in two forms 1) a particulate form, which is membrane bound, and 2) a soluble form. 

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