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)

Our previous studies in isolated endothelium-removed calf pulmonary arteries suggest that PO2-elicited responses are primarily mediated through modulation of guanosine 3',5'-cyclic monophosphate via changes in the generation of H2O2 originating from superoxide anion (O2-.) produced by NADH oxidase activity. In the present study we examined the importance of this mechanism in PO2-elicited responses of endothelium-removed calf coronary arteries. NADH oxidase activity was found to be the major source of O2-. in the homogenate of endothelium-removed calf coronary arteries detected by lucigenin-elicited chemiluminescence. Precontracted endothelium-removed calf coronary arteries show a relaxation to hypoxia, and reoxygenation causes a transient additional relaxation before the recovery of normoxic levels of force. Under these conditions the detection of O2-. was decreased by hypoxia and a transient overproduction was observed during reoxygenation. The relaxation to reoxygenation, but not to hypoxia, was significantly inhibited by a scavenger of O2-. that prevents the formation of H2O2 (nitro blue tetrazolium), an inhibitor of NAD(P)H oxidases and other O2(-.)-generating flavoproteins (diphenyliodonium), and inhibition of the stimulation of soluble guanylate cyclase (LY-83583). A scavenger of O2-. that promotes H2O2 formation (Tiron) did not inhibit the PO2-elicited responses examined. Hypoxia and diphenyliodonium (but not Tiron) decreased the metabolism of endogenous H2O2 by catalase (as measured by the H2O2-dependent co-oxidation of methanol to formaldehyde by catalase), and reoxygenation caused a stimulation of H2O2 metabolism by catalase. The presence of endothelium resulted in minor modifications of the PO2 responses, which were partially mediated via prostaglandins and nitric oxide on the basis of the effects of indomethacin and nitro-L-arginine, respectively. These results suggest that in calf coronary arteries the stimulation of guanylate cyclase via H2O2 originating from NADH-derived O2-(.) production contributes to the transient relaxation to posthypoxic reoxygenation, but not the response to hypoxia.
 ...
PMID:Oxygen-elicited responses in calf coronary arteries: role of H2O2 production via NADH-derived superoxide. 878 Feb 2

Our previous studies on the mechanism of relaxation of calf pulmonary arteries to H2O2 detected a role for increased formation of guanosine-3',5'-cyclic monophosphate as a result of a catalase-elicited activation of soluble guanylate cyclase. We have also shown that lactate elicits relaxation through increasing H2O2 produced from NADH oxidase-derived superoxide anion (O2-.). Because nitric oxide (NO) is a potential inhibitor of catalase, we examined the effects of exposure of endothelium-denuded bovine calf pulmonary arteries to an elevated physiological level of NO on relaxation to H2O2 and lactate. Treatment of pulmonary arteries with approximately 50 nM of NO gas for 2 min caused a subsequent inhibition of relaxation to H2O2 (10(-6) to 10(-3)M) and lactate (1-10 mM), without markedly altering relaxation responses to S-nitroso-N-acetylpenicillamine (10(-9) to 10(-6) M) or isoproterenol (10(-9) to 10(-6) M). This NO exposure caused a 63 and 70% inhibition of the metabolism by smooth muscle catalase of both endogenously produced and exogenous (100 microM) H2O2, respectively, as measured by the H2O2-dependent cooxidation of methanol to formaldehyde. A similar treatment of purified catalase with NO caused subsequent inhibition of its ability to metabolize H2O2, associated with changes in the spectra of catalase (increases in the absorbance at 535 and 570 nm) to a species that resembled compound II, an inactive form of catalase. The exposure of pulmonary arteries to NO also resulted in the detection of H2O2 release (by catalase-inhibitable luminol/ peroxidase-chemiluminescence). Thus exposure of pulmonary arteries to increased physiological levels of NO may promote altered vasoactive responses involving H2O2 as a result of the inhibition of catalase.
 ...
PMID:Nitric oxide inhibits pulmonary artery catalase and H2O2-associated relaxation. 894 7

The heat-stable enterotoxins (STs) produced by enterotoxigenic Escherichia coli are classified into two groups, methanol-soluble (STI) and methanol-insoluble (STII) enterotoxins. These are distinct toxins with unique properties. Their features in common include heat-stability, low molecular weight, secretion from the bacteria, and ability to induce fluid secretion from the intestine. STI is an 18- or 19-amino acid extracellular peptide with three intramolecular disulfide bonds, which is produced by proteolytic cleavage of 72 amino acid precursor. The STI in the lumen of the intestine binds to specific protein receptors (guanylate cyclase C) located in the brush border membrane and leads to elevation of intracellular cyclic GMP level. Several factors involved in the activation of guanylate cyclase by STI have been identified. Elevation of cyclic GMP level induces intestinal fluid secretion by stimulation of chloride secretion. Cystic fibrosis transmembrane conductance regulator, which is a chloride channel, might be involved in chloride secretion. In contrast, STII is a 48-amino acid peptide with two intramolecular disulfide bonds, which results from 71 amino acid precursor. Compared with STI, the steps that lead to intestinal fluid secretion by STII are not well established. It has been proposed that sulfatide in the brush border is a receptor for STII and that the STII bound to the receptor opens GTP-binding regulatory protein-linked calcium channels. These actions of STII induce not only stimulation of the production of secretagogues such as prostaglandin E2 and serotonin, but also activation of the calcium-calmodulin-dependent protein kinase II in the cells.
 ...
PMID:Properties and actions of heat-stable enterotoxin of Escherichia coli. 1099 26

The cardiovascular effect of the crude methanol extract from the leaf of Muntingia calabura L. (Tiliaceae) was investigated in the anesthetized rats. The crude methanol extract was sequentially fractionated to obtain the water-soluble extract (WSE). Intravenous administration of the WSE (10, 25, 50, 75 or 100 mg/kg) produced an initial followed by a delayed decrease in systemic arterial pressure (SAP) in a dose-dependent manner. The M. calabura-induced initial hypotension lasted for 10 min and the delayed depressor effect commenced after 90 min and lasted for at least 180 min post-injection. The same treatment, on the other hand, had no appreciable effect on heart rate (HR) or the blood gas/electrolytes concentrations. Both the initial and delayed hypotensive effects of WSE (50 mg/kg, i.v.) were significantly blocked by pre-treatment with a nonselective nitric oxide (NO) synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester ((L)-NAME, 0.325 mg/kg/min for 5 min) or a soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazole[4,3-alpha]quinoxalin-1-one (ODQ, 0.2 mg/kg/min for 5 min). Moreover, whereas the initial depressor effect of WSE was inhibited by pre-treatment with a selective endothelial NOS (eNOS) inhibitor, N5-(1-Iminoethyl)-L-ornithine ((L)-NIO, 1 mg/kg/min for 5 min), the delayed hypotension was attenuated by a selective inducible NOS (iNOS) inhibitor, S-methylisothiourea (SMT, 0.5 mg/kg/min for 5 min). Administration of WSE also produced an elevation in plasma nitrate/nitrite concentration, as well as an increase in the expression of iNOS protein in the heart and thoracic aorta. These results indicate that WSE from the leaf of M. calabura elicited both a transient and delayed hypotensive effect via the production of NO. Furthermore, activation of NO/sGC/cGMP signaling pathway may mediate the M. calabura-induced hypotension.
 ...
PMID:Activation of nitric oxide signaling pathway mediates hypotensive effect of Muntingia calabura L. (Tiliaceae) leaf extract. 1708 May 50

Vasodilators are important pharmacologic agents for managing and/or treating hypertension. Medicinal plants are considered as valuable source of bioactive compounds. We used a bioguided approach to isolate, identify, and investigate the possible vasodilation activities and mechanism(s) of the prepared methanol extract from aerial parts of Psiadia punctulata (MAPP), its bioactive fraction and active compounds. Vascular effects of MAPP were studied using isolated artery technique in the presence or absence of specific candidate pathways inhibitors, and found to produce a significant vasodilation of phenylephrine preconstricted rat aortae. The bioactive chloroform fraction yielded five methoxylated flavonoids: umuhengerin (1), gardenin A (2), gardenin B (3), luteolin-3',4' -dimethyl ether (4), and 5,3'-dihydroxy-6,7,4',5'-tetramethoxyflavone (5). Metabolites 1, 4, and 5 produced a significant vasodilation. Removal of the endothelium significantly inhibited MAPP vasodilation. Nitric oxide synthase inhibition and not prostacycline inhibition or K+ channel blocking, was found to cause the observed vasodilation inhibition. Both guanylate cyclase and adenylate cyclase inhibitions markedly inhibited MAPP vasodilation. In conclusion MAPP possesses vasodilation activities that is mediated through endothelial nitric oxide pathway, calcium dependent endothelial nitric oxide synthase activation, and interference with the depolarization process through calcium channel blocking activity.
 ...
PMID:Major flavonoids from Psiadia punctulata produce vasodilation via activation of endothelial dependent NO signaling. 3238 47


<< Previous 1 2