Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was hypothesized that hypoxia may inhibit nitric oxide (NO) production by reducing the availability of endothelial NO synthase (NOS III) substrate. To evaluate the effect of L-arginine on the NO release in high altitude, 11 subjects were infused with L-arginine (0.5 g x kg(-1)) during 30 min in normoxia and after 36 h at 4,350 m (hypoxia). The L-citrulline and cyclic guanosine monophosphate (cGMP) concentrations were measured to investigate NO synthesis and guanylyl cyclase activity respectively. L-citrulline concentration, arterial oxygen saturation (Sa,O2), systemic blood pressure, heart rate and acute mountain sickness (AMS) score were measured at rest and 15, 30 and 45 min after starting infusion. The results showed that baseline L-citrulline was lower in hypoxia (p<0.05). L-arginine infusion increased L-citrulline concentration in both conditions. However, in hypoxia L-citrulline concentration remained lower than in normoxia (p<0.05). The concentration of cGMP was lower in hypoxia (p<0.05). In hypoxia, Sa,O2 increased from 15 min after the start of the infusion to 45 min (p<0.05). Blood pressure and heart rate were not affected by L-arginine infusion. Subjects who experienced symptoms of AMS showed a slight decrease in AMS score with L-arginine. The decreased L-citrulline suggests a hypoxia-induced impairment of nitric oxide synthase III or a decrease in L-arginine availability. The improvement of arterial oxygen saturation by pretreatment with L-arginine could be ascribed to an enhancement of the ventilation/perfusion ratio. Collectively, these results are consistent with a decrease in nitric oxide production in hypoxia that could be antagonized by supplying nitric oxide synthase cosubstrate.
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PMID:Response of nitric oxide pathway to L-arginine infusion at the altitude of 4,350 m. 1152 86

In A7r5 vascular smooth muscle cells vasopressin, via arachidonic acid, regulates two Ca(2+)-entry pathways. Capacitative Ca(2+) entry (CCE), activated by empty Ca(2+) stores, is inhibited by arachidonic acid, and non-capacitative Ca(2+) entry (NCCE) is stimulated by it. This reciprocal regulation ensures that all Ca(2+) entry is via NCCE in the presence of vasopressin, while CCE mediates a transient Ca(2+) entry only after removal of vasopressin. We demonstrate that type III NO synthase (NOS III) is expressed in A7r5 cells and that NO inhibits CCE. Inhibition of CCE by vasopressin requires NOS III and the requirement lies downstream of arachidonic acid. Activation of soluble guanylate cyclase by NO and subsequent activation of protein kinase G are required for inhibition of CCE. Stimulation of NCCE by vasopressin also requires NOS III, but the stimulation is neither mimicked by cGMP nor blocked by inhibitors of soluble guanylate cyclase or protein kinase G. We conclude that arachidonic acid formed in response to vasopressin stimulates NOS III. NO then directly stimulates Ca(2+) entry through NCCE and, via protein kinase G, it inhibits CCE. The additional amplification provided by the involvement of guanylate cyclase and protein kinase G ensures that CCE will always be inhibited when vasopressin activates NCCE.
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PMID:Nitric oxide co-ordinates the activities of the capacitative and non-capacitative Ca2+-entry pathways regulated by vasopressin. 1245 38

The epithelial rests of Malassez (ERM) are derived from the disintegrating epithelial root sheath of Hertwig that guides root formation during tooth development. Low concentrations of nitric oxide (NO) produced by NO-synthase I (NOS I) and NOS III activate intracellular soluble guanylate cyclase (sGC) to produce intracellular cyclic guanosine 3':5'-monophosphate (cGMP), which triggers rapid cellular responses such as cell proliferation, cell differentiation, and apoptosis under physiological conditions. The presence of NOS I-III, sGC (alpha2- and beta1-subunits) and cGMP in the ERM was investigated by immunohistochemistry. Rat molars with periodontium were perfusion and postfixed, decalcified, frozen-sectioned, and sections were immunostained. NOS I, NOS III, sGC (alpha2- and beta1-subunits) and cGMP were localized with different densities in the ERM. The presence of NOS II in the ERM varied. The localization of NOS I, NOS III, sGC and cGMP in the ERM indicates an involvement of NO and/or NO-cGMP signal pathway molecules in homeostasis of a variety of physiological processes in the ERM. These could include regulation of cell proliferation, cell differentiation and apoptosis.
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PMID:NO-cGMP signaling molecules in the rat epithelial rests of Malassez. 1487 Nov 94