Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of endotoxin on endothelial and smooth muscle function were investigated in small femoral arteries removed from rats 4 h after intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS; 20 mg/kg) or solvent. In the absence of L-arginine in the organ bath, the sensitivity of the arteries to norepinephrine (NE) was decreased only slightly, and the relaxing effects of neither 3-morpholinosydonimine-N-ethyl-carbamide (SIN-1), a nitric oxide (NO) donor, nor acetylcholine (ACh) were modified by LPS treatment despite morphological damage to the endothelium seen with scanning electron microscopy. However, L-arginine (30 microM to 1 mM), which had no effect on control vessels, caused a rapid and stereospecific relaxation of arteries from LPS-treated rats that was abolished by both NG-nitro-L-arginine methyl ester (1 mM), a NO synthase inhibitor, and methylene blue, an inhibitor of the activation of guanylyl cyclase by NO. The relaxing effect of L-arginine was observed in the absence of endothelium, although it was significantly greater in its presence. In addition, a 30-min exposure to extracellular L-arginine (100 microM) moderately but significantly decreased the sensitivity to ACh and SIN-1 of vessels from LPS-treated but not from control rats. These results indicate that LPS treatment induced a NO synthase activity in smooth muscle cells of rat small femoral arteries and that the resulting relaxation was dependent on extracellular L-arginine in these resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effect of bacterial lipopolysaccharide on function of rat small femoral arteries. 830 99

Experiments were designed to determine the role of the L-arginine pathway in endothelium-dependent relaxations to vasopressin. The effects of L-arginine analogues NG-nitro-L-arginine (L-NNA), NG-nitro-L-arginine methyl ester (L-NAME), and NG-monomethyl-L-arginine (L-NMMA) on basal and vasopressin-induced activity of nitric oxide synthase were studied in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (37 degrees C, pH 7.4). Radioimmunoassay was used to determine the level of guanosine 3',5'-cyclic monophosphate (cGMP). All experiments were performed in the presence of indomethacin, a cyclooxygenase inhibitor. L-NAME and L-NMMA caused endothelium-dependent contractions and inhibited basal production of cGMP. In contrast, L-NNA did not affect basal tone or basal production of cGMP. L-Arginine analogues inhibited relaxations to vasopressin but did not affect relaxations to a nitric oxide donor, molsidomine (SIN-1). The effects of L-NNA, L-NAME, and L-NMMA were reversed in the presence of L-arginine. The relaxations to vasopressin were associated with an increase of cGMP levels in the arterial wall. This effect of vasopressin was inhibited in the presence of L-NNA. These studies suggest that the relaxations to vasopressin are mediated by activation of the endothelial L-arginine pathway, leading to increased production of nitric oxide, with subsequent activation of guanylate cyclase in smooth muscle cells. In canine basilar artery, L-NAME and L-NMMA are nonselective inhibitors of both basal and stimulated production of nitric oxide, whereas L-NNA selectively inhibits vasopressin-induced activation of the L-arginine pathway.
...
PMID:Endothelial L-arginine pathway and relaxations to vasopressin in canine basilar artery. 838 55

This study aimed to examine the role of nitric oxide (NO) in the regulation of renin secretion from renal juxtaglomerular (JG) cells. Using primary cultures of mouse renal JG cells, we found that sodium nitroprusside (SNP) and 3-morpholino-sydnonimin-hydrochloride (SIN-1), two structurally different liberators of NO, led to a transient inhibition during the first hour followed by a marked dose-dependent stimulation of renin secretion lasting for an additional 20 h. This stimulatory effect was blunted by methylene blue (50 microM) and was reversible within minutes after removal of the NO liberators. SNP and SIN-1 also stimulated guanylate cyclase activity in the cultures with a maximum within the first hour of incubation. Increasing intracellular guanosine 3',5'-cyclic monophosphate levels by 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (100 microM) or by atrial natriuretic peptide (10 nM) decreased basal renin secretion but did not inhibit the effect of SNP. The stimulatory effect of SNP was not related to adenosine 3',5'-cyclic monophosphate levels in the JG cells and was blunted after chelation of extracellular calcium by 2 mM ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N'N'-tetraacetic acid. Taken together, our findings suggest that liberators of NO have two effects on renin secretion from isolated JG cells: an inhibitory effect mediated by stimulation of soluble guanylate cyclase activity and a stimulatory effect mediated by an as yet unknown pathway that requires extracellular calcium.
...
PMID:Liberators of NO exert a dual effect on renin secretion from isolated mouse renal juxtaglomerular cells. 839 40

The effects of the NO-donor 3-morpholinosydnonimin (SIN-1) on isometric tension, cyclic guanosine 3',5'-monophosphate (cyclic GMP) accumulation and neuronal release of 3H-noradrenaline were investigated in rabbit isolated corpus cavernosum (CC), and compared to the actions of sodium nitroprusside (SNP) and the cyclic GMP-specific phosphodiesterase inhibitor zaprinast. SIN-1, zaprinast and SNP concentration dependently relaxed rabbit CC preparations contracted by 1 microM. phenylephrine. All the drugs were highly effective, and the order of potency was SNP > zaprinast > SIN-1. SIN-1 had a biphasic effect on contractions evoked by electrical field stimulation of nerves: at low concentrations (1 and 10 microM.), SIN-1 inhibited the contractions, while at concentrations > or = 100 microM., the contractions were again increased. There were no changes in baseline tension. Electrically evoked contractions were inhibited by zaprinast in a concentration-dependent manner. Compared with controls, 1 mM. SIN-1 caused a significant (p < 0.05) increase in both the basal efflux and in the electrically induced release of 3H from CC preparations incubated with 3H-noradrenaline. SIN-1, zaprinast and SNP increased tissue levels of cyclic GMP. There was no positive correlation between cyclic GMP accumulation and the relaxant effects of the drugs. The effects of SIN-1 and SNP on the tissue content of cyclic GMP were not significantly affected by methylene blue, an inhibitor of soluble guanylate cyclase. It may be concluded that SIN-1, zaprinast and SNP are effective in relaxing isolated penile erectile tissue, and this effect is associated with an increase in the tissue content of cyclic GMP via pathways not sensitive to methylene blue. However, additional mechanisms beside stimulation of adrenergic neurotransmission and activation of guanylate cyclase in the smooth muscle cell seem to participate in the action of SIN-1 on rabbit penile erectile tissue.
...
PMID:Actions of 3-morpholinosydnonimin (SIN-1) on rabbit isolated penile erectile tissue. 839 90

In the presence of 3-isobutyl-methylxanthine (IBMX), induction of cyclic 3',5'-guanosine monophosphate (GMP) production in human washed platelets (HWP) by nitric oxide donors (NOD) is followed by its accumulation in the surrounding medium in a time- and concentration-dependent manner. Thirty minutes incubation of HWP with 3-morpholino-sydonimine (SIN-1, 10 microM) at 37 degrees C resulted in a 4.6-fold increase of cyclic GMP in platelets, whereas in the extracellular medium the increase was 17.6-fold. Similar results were obtained when other NOD such as S-nitroso-N-acetylpenicyllamine (SNAP) and 3-(2-methoxy-5-chlorophenyl)oxatriazol-5-imine (GEA 3184) and the selective phosphodiesterase inhibitor, zaprinast (M&B 22948, 10 microM), were used. Probenecid (1-300 microM), an inhibitor of organic anion transport, or ouabain (1-300 microM), an inhibitor of Na+/K+ adenine triphosphate (ATP)-ase had no effect on cyclic GMP production or extrusion after stimulation with SIN-1. Significantly prostaglandin A1 (PGA1) and prostaglandin D2 (PGD2) inhibited the efflux of cyclic GMP from platelets induced by SNAP (10 microM) in a concentration-dependent fashion, with an IC50 of 63 +/- 16 and 143 +/- 17 microM, respectively. These studies suggest that the extrusion of cyclic GMP from human platelets after activation of soluble guanylate cyclase by NOD may contribute to the control of cyclic GMP levels in platelets with potential physiological and therapeutic consequences.
...
PMID:Nitric oxide donors induce extrusion of cyclic GMP from isolated human blood platelets by a mechanism which may be modulated by prostaglandins. 858 70

We investigated, using rat brain cortex supernatant as a source of guanylate cyclase (GC), whether sodium nitroprusside (SNP) can not only activate but also inhibit GC. SNP (I and 10 microM) activated the rat brain GC; however, at higher concentrations GC activation was reduced, resulting in a bell-shaped concentration-activation curve. Preincubation of GC with 10 microM SNP attenuated GC activation by SNP, S-nitroso-N-acetylpenicillamine (SNAP) or 3-morpholinosydnonimine-N-ethyl-carbamine (SIN). Such inhibitory effects of SNP were partially supressed by a nitric oxide (NO) scavenger oxyhemoglobin. The preincubation of GC with K4Fe(CN)6 (a carrier molecule for SNP but devoid of NO) had no inhibitory effects on GC activation. These results indicate that SNP, probably through NO, has dual effects on GC activity, stimulation and inhibition.
...
PMID:Stimulatory and inhibitory effects of sodium nitroprusside on soluble guanylate cyclase. 860 15

We examined the role of endogenous NO in the autonomic regulation of atrioventricular (AV) nodal function by studying spontaneous action potentials (SAPs) and L-type Ca2+ current (ICa-L) in isolated single AV nodal cells from adult rabbit hearts. Both the perforated and the membrane-ruptured patch-clamp techniques in the whole-cell configuration were used under conditions known to alter NO production. Three NO donors, 3-morpholinosydnonimine (SIN-1, 0.1 mmol/L), S-nitroso-acetylcysteine (0.1 mmol/L), and sodium nitroprusside (0.1 mmol/L), suppressed the beta-adrenergic agonist isoproterenol (ISO, 1 mumol/L)-stimulated increase in ICa-L. SIN-1 also decreased the frequency and amplitude of SAPs. In cells in which ICa-L had been previously attenuated by the muscarinic agonist carbamylcholine (CCh, 1 mumol/L), SIN-1 had no additive effect. CCh activated an acetylcholine-sensitive outward K+ current (IK(ACh)) in AV nodal cells, in addition to the ICa-L inhibition. Intracellular dialysis with the NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA, 0.5 mmol/L) blocked CCh-induced, but not SIN-1-induced, ICa.L attenuation. However, intracellular dialysis with methylene blue (20 mumol/L), which inhibits NO-mediated activation of guanylyl cyclase and cGMP production, blocked the effects of both CCh and SIN-1 on ICa-L. In these cells, neither L-NMMA nor methylene blue affected the CCh-activated IK(ACh). Direct application of cGMP (10 mumol/L) via internal dialysis significantly inhibited ISO-stimulated ICa-L. In AV nodal cells internally perfused with either a nonhydrolyzable cAMP analogue, 8-Br-cAMP (0.5 mmol/L), or a high concentration of cAMP (0.5 mmol/L), CCh did not inhibit, ICa-L but still activated IK(ACh). CCh-induced ICa-L attenuation could be abolished or quickly reversed by the nonselective phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (20 mumol/L). However, CCh still significantly suppressed ISO-stimulated ICa-L after the cGMP-inhibited PDE isozyme (PDE3) had been selectively inhibited by milrinone (5 mumol/L). Immunohistochemical staining identified the presence of the endothelial constitutive NO synthase (ecNOS or NOS3) in both single AV nodal cells in vitro and in cryostat sections of AV nodal tissue in situ. These results demonstrate that endogenous NO is involved in the muscarinic cholinergic attenuation of ICa-L in AV nodal cell; the mechanism likely involves the cGMP-stimulated PDE.
...
PMID:Nitric oxide synthase (NOS3)-mediated cholinergic modulation of Ca2+ current in adult rabbit atrioventricular nodal cells. 863 50

The effects of the K+ channel blockers, apamin, tetraethylammonium and 4-aminopyridine, upon the relaxations of the isolated rat proximal duodenum induced by nitregic nerve activation, nitric oxide (NO), the NO donor 3-morpholinosydnonimine (SIN-1) and Br-cyclic GMP were determined. The effects of the guanylate cyclase inhibitors, cystamine and N-methylhydroxylamine, on NO-, SIN-1- and nitrergic nerve-induced responses were also investigated. Apamin inhibited nitrergic nerve-, NO-and SIN-1-induced relaxations but did not affect those induced by Br-cGMP. Tetraethylammonium and 4-aminopyridine as well as cystamine and N-methylhydroxylamine failed to affect the relaxations caused by any of the agents tested. These findings indicate that, in the rat proximal duodenum, nitrergic nerve activation as well as exogenous nitric oxide cause relaxation through a cGMP-independent, apamin sensitive mechanism.
...
PMID:Rat duodenum nitrergic-induced relaxations are cGMP-independent and apamin-sensitive. 866 8

Left ventricular hypertrophy (LVH) produced by aortic valve plication leads to increased myocardial cyclic GMP. We tested whether this was a result of increased soluble guanylate cyclase activity or nitric oxide (NO) synthase and its functional consequences. We used the nitric oxide donor 3-morpholino-sydnonimine (SIN-1) or the NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME) in 12 control and 12 LVH anesthetized open-chest mongrel dogs. L-NAME (6 mg/kg) or SIN-1 (1 microgram/kg per min) was infused into the left anterior descending coronary artery and regional segment work and cyclic GMP levels were determined. In vitro myocardial guanylate cyclase sensitivity (0.43 +/- 0.04 to 0.28 +/- 0.04 mM [EC50]) and maximal activity (10.1 +/- 2.9 to 25.5 +/- 6.5 pmol/mg protein per min) were significantly increased in LVH as compared with control animals in response to nitroprusside stimulation, but cyclic GMP-phosphodiesterase activity was similar. In LVH dogs, basal cyclic GMP was significantly elevated in vivo when compared with controls. Treatment of dogs with SIN-1 resulted in a significant increase in cyclic GMP in control (1.09 +/- 0.12 to 1.48 +/- 0.19 pmol/gram) and a greater increase in the LVH group (1.78 +/- 0.16 to 3.58 +/- 0.71 pmol/g). L-NAME had no effect on myocardial cyclic GMP levels in control or LVH dogs. Segment work decreased in the control group after SIN-1 (1,573 +/- 290 to 855 +/- 211 grams x mm/min). LVH dogs showed no decrement in work as a result of treatment with SIN-1. L-NAME did not cause significant changes in myocardial cyclic GMP, O2 consumption, or work in either control or LVH dogs, but vascular effects were evident. SIN-1 increased cyclic GMP, and with greater effect on LVH; however, this resulted in a decrement in function only in the control group. The greater increased cyclic GMP in LVH dogs is not related to increased NO production, but is related to significantly higher sensitivity and maximal activity of soluble myocardial guanylate cyclase.
...
PMID:Increased guanylate cyclase activity is associated with an increase in cyclic guanosine 3',5'-monophosphate in left ventricular hypertrophy. 869 76

Nitric oxide (NO) produced opposite effects on acetylcholine (ACh) release in identified neuroneuronal Aplysia synapses depending on the excitatory or the inhibitory nature of the synapse. Extracellular application of the NO donor, SIN-1, depressed the inhibitory postsynaptic currents (IPSCs) and enhanced the excitatory postsynaptic currents (EPSCs) evoked by presynaptic action potentials (1/60 Hz). Application of a membrane-permeant cGMP analog mimicked the effect of SIN-1 suggesting the participation of guanylate cyclase in the NO pathway. The guanylate cyclase inhibitor, methylene blue, blocked the NO-induced enhancement of EPSCs but only reduced the inhibition of IPSCs indicating that an additional mechanism participates to the depression of synaptic transmission by NO. Using nicotinamide, an inhibitor of ADP-ribosylation, we found that the NO-induced depression of ACh release on the inhibitory synapse also involves ADP-ribosylation mechanism(s). Furthermore, application of SIN-1 paired with cGMP-dependent protein kinase (cGMP-PK) inhibitors showed that cGMP-PK could play a role in the potentiating but not in the depressing effect of NO on ACh release. Increasing the frequency of stimulation of the presynaptic neuron from 1/60 Hz to 0.25 or 1 Hz potentiated the EPSCs and reduced the IPSCs. In these conditions, the potentiating effect of NO on the excitatory synapse was reduced, whereas its depressing effect on the inhibitory synapse was unaffected. Moreover the frequency-dependent enhancement of ACh release in the excitatory synapse was greatly reduced by the inhibition of NO synthase. Our results indicate that NO may be involved in different ways of modulation of synaptic transmission depending on the type of the synapse including synaptic plasticity.
...
PMID:Opposite actions of nitric oxide on cholinergic synapses: which pathways? 871 Sep 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---