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)

The administration of oestrogens increases the hepatic synthesis and plasma level of ceruloplasmin both in man and laboratory animals. Methylene blue, an oxidizing agent and inhibitor of soluble guanylate cyclase, is widely used to block the effects of endothelium-derived relaxing factor (nitric oxide). We describe the inhibitory effect of methylene blue on the increase of ceruloplasmin plasma level in rats during oestradiol treatment.
 ...
PMID:Methylene blue inhibition of oestradiol-induced increase of ceruloplasmin serum levels in rats. 784 Nov 67

Methylene blue (MB) is a thiazine dye used in the treatment of methemoglobinemia. It may represent a new class of anti-oxidant drugs which competitively inhibit the reduction of molecular oxygen to superoxide by acting as an alternative electron acceptor for tissue oxidases. Because of its strong free radicals scavenging effect MB was experimentally used in the treatment of reperfusion syndrome. MB is soluble guanylate cyclase inhibitor. It was found to inhibit the stimulation of soluble guanylate cyclase by nitric oxide and vasodilatators. Another effect of MB is inhibition of prostacyclin synthesis by endothelial cells and isolated arteries independently of its effects on cGMP accumulation. We investigated the MB in series of experimental endocrine situations in which its free radicals scavenging effect could play a role. We observed that MB partly inhibited the increase in adenohypophyseal weight, cAMP and blood prolactin levels in male rats after the administration of estrogens. MB also blocked the increase of another free radicals scavenger-the metalloenzyme ceruloplasmin in the blood of estrogenized rats and prevented the increase of bone mineral after estradiol treatment. MB produced a decrease in adenohypophyseal ascorbic acid content. The blood thyroxine levels increased and the anterior pituitary TSH concentration decreased after MB treatment.
 ...
PMID:Methylene blue--an endocrine modulator. 871 76

1. Nitric oxide (NO) is a potent inhibitor of platelet activation, that inhibits the agonist-induced increase in cytosolic Ca2+ concentration through both cGMP-dependent and independent pathways. However, the NO-related (NOx) species responsible for cGMP-independent signalling in platelets is unclear. We tested the hypothesis that extracellular NO, but not NO+ or peroxynitrite, generated in the extracellular compartment is responsible for cGMP-independent inhibition of platelet activation via inhibition of Ca2+ signalling. 2. Concentration-response curves for diethylamine diazeniumdiolate (DEA/NO; a spontaneous NO generator), S-nitroso-N-valerylpenicillamine (SNVP; an S-nitrosothiol) and 3-morpholinosydnonomine (SIN-1; a peroxynitrite generator) were generated in platelet-rich plasma (PRP) and washed platelets (WP) in the presence and absence of a supramaximal concentration of the soluble guanylate cyclase inhibitor, ODQ (20 microM). All three NOx donors displayed cGMP-independent inhibition of platelet aggregation in PRP, but only DEA/NO exhibited cGMP-independent inhibition of aggregation in WP. 3. Analysis of NO generation using an isolated NO-electrode revealed that cGMP-independent effects coincided with the generation of substantial levels of extracellular NO (>40 nM) from the NOx donors. 4. Reconstitution of WP with plasma factors indicated that the copper-containing plasma protein, caeruloplasmin (CP), catalysed the release of NO from SNVP, while Cu/Zn superoxide dismutase (SOD) unmasked NO generated from SIN-1. The increased generation of extracellular NO correlated with a switch to cGMP-independent effects with both NOx donors. 5. Analysis of Fura-2 loaded WP revealed that only DEA/NO inhibited Ca2+ signalling in platelets via a cGMP-independent mechanism. However, preincubation of SNVP and SIN-1 with CP and SOD, respectively, induced cGMP-independent inhibition of intraplatelet Ca2+ trafficking by the NOx donors. 6. Taken together, our data suggest that extracellular NO (>40 nM) is required for cGMP-independent inhibition of platelet activation. Plasma constituents may play an important pharmacological role in activating cGMP-independent signalling by S-nitrosothiols or peroxynitrite generators.
 ...
PMID:A potential role for extracellular nitric oxide generation in cGMP-independent inhibition of human platelet aggregation: biochemical and pharmacological considerations. 1568 9

Protein and peptide S-nitrosothiols (SNOs) are involved in guanylate cyclase-independent signaling associated with nitric oxide synthase (NOS) activation. As a general rule, SNO formation requires the presence of an electron acceptor such as Cu2+. Various proteins have been identified that catalyze SNO formation, including NOS itself, ceruloplasmin, and hemoglobin. Biochemical evidence suggests the existence of other SNO synthases and NOS-associated proteins involved in SNO formation following NOS activation. Indeed, both hydrophilic and hydrophobic consensus motifs have been identified that favor protein S-nitrosylation. Inorganic SNO formation appears also to occur in biological systems at low pH levels and/or in membranes. Once formed, SNOs localized to specific cellular compartments signal specific effects, ranging from gene regulation to ion channel gating. Indeed, the number of cellular and physiological functions appreciated to be regulated through SNO synthesis, localization, and catabolism is increasing. Although research into SNO biosynthesis is in its infancy, the importance of this field of biochemistry has been confirmed repeatedly by investigators from a broad spectrum of disciplines.
 ...
PMID:S-nitrosothiol formation. 1629 Dec 25