Search results for "Soluble Guanylyl Cyclase"
showing 10 items of 51 documents
Effects of nitric oxide donors on cardiac contractility in wild-type and myoglobin-deficient mice
2002
1. The effects of the nitric oxide (NO) donors S-nitroso-N-acetylpenicillamine (SNAP), sodium(Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA-NONOate), and (Z)-1-[N-(2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate) on force of contraction (F(c)) were studied in atrial and ventricular muscle strips obtained from wild-type (WT) and myoglobin-deficient (myo(-/-)) mice. 2. SNAP slightly reduced F(c) in preparations from WT mice at concentrations above 100 microM; this effect was more pronounced in myo(-/-) mice. 3. DEA-NONOate reduced F(c) in preparations from myo(-/-) mice to a larger extent than those from WT mice. 4. DETA-NONOate reduced F(c) in preparations…
Modulation of acetylcholine release in the guinea-pig trachea by the nitric oxide donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP)
2000
The effects of the nitric oxide (NO) donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) and the NO synthase inhibitor L-N(G)-nitroarginine (L-NOARG) on the electrically evoked [(3)H]-acetylcholine release were studied in an epithelium-free preparation of guinea-pig trachea that had been preincubated with [(3)H]-choline. SNAP (100 and 300 microM) caused small but significant increases of the electrically evoked [(3)H]-acetylcholine release (121+/-4% and 124+/-10% of control). Resting outflow of [(3)H]-ACh was not affected by SNAP. The increase by SNAP was abolished by the specific inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 1 microM). The facili…
Explaining the phenomenon of nitrate tolerance.
2005
During the last century, nitroglycerin has been the most commonly used antiischemic and antianginal agent. Unfortunately, after continuous application, its therapeutic efficacy rapidly vanishes. Neurohormonal activation of vasoconstrictor signals and intravascular volume expansion constitute early counter-regulatory responses (pseudotolerance), whereas long-term treatment induces intrinsic vascular changes, eg, a loss of nitrovasodilator-responsiveness (vascular tolerance). This is caused by increased vascular superoxide production and a supersensitivity to vasoconstrictors secondary to a tonic activation of protein kinase C. NADPH oxidase(s) and uncoupled endothelial nitric oxide synthase …
Immuno-electron microscopic localization of the alpha(1) and beta(1)-subunits of soluble guanylyl cyclase in the guinea pig organ of corti.
2000
Guanylyl cyclases (GC) catalyze the formation of the intracellular signal molecule cyclic GMP from GTP. For some years it has been known that the heme-containing soluble guanylyl cyclase (sGC) is stimulated by NO and NO-containing compounds. The sGC enzyme consists of two subunits (alpha(1) and beta(1)). In the present study, the alpha(1) and beta(1)-subunits were identified in the guinea pig cochlea at the electron microscopic level using a post-embedding immuno-labeling procedure. Ultrathin sections of LR White embedded specimens were incubated with various concentrations of two rabbit polyclonal antibodies to the alpha(1)- and beta(1)-subunit, respectively. The immunoreactivity was visua…
Functional coupling of nitric oxide synthase and soluble guanylyl cyclase in controlling catecholamine secretion from bovine chromaffin cells
1997
This study was designed to evaluate whether the enzymes of the nitric oxide/cyclic-GMP pathway, nitric oxide synthase and soluble guanylyl cyclase, are functionally coupled in controlling catecholamine secretion in primary cultures of bovine chromaffin cells. In immunocytochemical studies, 80-85% of the tyrosine hydroxylase-positive chromaffin cells also possessed phenylethanolamine-N-methyltransferase, f1p4cating their capability to synthesize epinephrine. Immunoreactivity for neuronal-type nitric oxide synthase was found in over 90% of all chromaffin cells. Reverse transcription-polymerase chain reaction also demonstrated neuronal-type nitric oxide synthase messenger RNA. Immunoreactivity…
Nitric oxide increases the decay of matrix metalloproteinase 9 mRNA by inhibiting the expression of mRNA-stabilizing factor HuR.
2003
Dysregulation of extracellular matrix turnover is an important feature of many inflammatory processes. Rat renal mesangial cells express high levels of matrix metalloproteinase 9 (MMP-9) in response to inflammatory cytokines such as interleukin-1 beta. We demonstrate that NO does strongly destabilize MMP-9 mRNA, since different luciferase reporter gene constructs containing the MMP-9 3' untranslated region (UTR) displayed significant reduced luciferase activity in response to the presence of NO. Moreover, by use of an in vitro degradation assay we found that the cytoplasmic fractions of NO-treated cells contained a higher capacity to degrade MMP-9 transcripts than those obtained from contro…
Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress
2015
Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of…
Biochemistry and pharmacology of novel anthranilic acid derivatives activating heme-oxidized soluble guanylyl cyclase.
2005
The heme-enzyme soluble guanylyl cyclase (sGC) is an ubiquitous NO receptor, which mediates NO downstream signaling by the generation of cGMP. We studied the mechanism of action of the anthranilic acid derivatives 5-chloro-2-(5-chloro-thiophene-2-sulfonylamino-N-(4-(morpholine-4-sulfonyl)-phenyl)-benzamide sodium salt (HMR1766) (proposed international nonproprietary name, ataciguat sodium) and 2-(4-chloro-phenylsulfonylamino)-4,5-dimethoxy-N-(4-(thiomorpholine-4-sulfonyl)-phenyl)-benzamide (S3448) as a new class of sGC agonists. Both compounds activated different sGC preparations (purified from bovine lung, or crude from human corpus cavernosum) in a concentration-dependent and quickly reve…
A non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease
2018
Endothelial nitric oxide (NO) stimulates the heme protein, soluble guanylyl cyclase (sGC) to form vasoprotective cyclic GMP (cGMP). In different disease states such as pulmonary hypertension, NO-cGMP signaling is pharmacologically augmented, yet the pathomechanisms leading to its dysregulation are incompletely understood. Here we show in pulmonary artery endothelial cells that endogenous NO or NO donor compounds acutely stimulate sGC activity, but chronically down-regulate both sGC protein and cGMP formation. Surprisingly, this endogenous feedback mechanism was independent of canonical cGMP signaling via cGMP-dependent protein kinase. It did not involve thiol-dependent modulation, a process…
Antiproliferative effects of drugs affecting different signalling pathways on rat and human pulmonary artery smooth muscle cells
2015
Current treatments for pulmonary arterial hypertension (PAH) include pulmonary vasodilators which may also inhibit PASMC proliferation. The aim of this study was to compare the antiproliferative effects of multiple drugs on rat and human PASMC (rPASMC and hPMASC, respectively) in vitro. rPASMCs and hPASMC were starved for 24 h, then treated with different inhibitors and incubated for 48 h in 1% foetal calf serum plus endothelin-1, 5-HT and U46619. Cell number was estimated by the MTT test. Viable cells increased by 160-180% in 48 h. Activation of the cGMP pathway with the soluble guanylyl cyclase activators riociguat and YC-1 (≤ 10 µM) or the cAMP pathway by the adenylyl cyclase activator f…