Search results for "Cyclase"
showing 10 items of 141 documents
Activation of soluble guanylyl cyclase by YC-1 in aortic smooth muscle but not in ventricular myocardium from rat
1997
1 The effects of YC-1 (3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole), an activator of soluble guanylyl cyclase, on tension, levels of cyclic GMP and cyclic AMP, and cardiac L-type Ca2+-current (ICa(L)) were investigated in aortic smooth muscle and ventricular heart muscle from rat. 2 YC-1 (0.1–30 μM) induced a concentration-dependent relaxation in aortic rings precontracted with phenylephrine (3 μM). The relaxant effects of YC-1 were reversed by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (30 μM; ODQ), potentiated by zaprinast (10 μM) and antagonized by Rp-8-Br-cGMPS (100 μM). 3 In ventricular heart muscle strips, YC-1 (30 μM) exhibited no effects on force of contraction (Fc) in the abse…
The sGC stimulator riociguat inhibits platelet function in washed platelets but not in whole blood
2015
Background and Purpose Stimulation of soluble guanylyl cyclase (sGC) is a valuable therapeutic strategy for the treatment of several cardiovascular diseases. The sGC stimulator riociguat has been approved for the treatment of two forms of pulmonary hypertension. Platelets contain large amounts of sGC and play a key role in the regulation of haemostasis. Therefore, we investigated the effects of riociguat on platelet function. Experimental Approach The effect of riociguat treatment on human platelet activation and aggregation was investigated. The sGC-specific effects of riociguat were determined by comparing wild-type and platelet-specific sGC-knockout mice. Key Results Riociguat induced cG…
Different β-adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vesse…
2013
Background and Purpose To analyse the relative contribution of β1-, β2- and β3-adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways. Experimental Approach Rat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real-time-PCR and immunohistochemistry, and for the pharmacological characterization of Adrb-mediated activity by wire myography and tissue nucleotide accumulation. Key Results The mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP…
Role of central glutamate receptors, nitric oxide and soluble guanylyl cyclase in the inhibition by endotoxin of rat gastric acid secretion
2000
1. This study examines the role of a central pathway involving glutamate receptors, nitric oxide (NO) and cyclic GMP in the acute inhibitory effects of low doses of peripheral endotoxin on pentagastrin-stimulated acid production. 2. Vagotomy or intracisternal (i.c.) microinjections of the NO-inhibitor, N(G)-nitro-L-arginine methyl esther (L-NAME; 200 microg rat(-1)) restored acid secretory responses in endotoxin (10 microg kg(-1), i.v.)-treated rats. 3. The acid-inhibitory effect of i.v. endotoxin (10 microg kg(-1), i.v.) was prevented by prior i.c. administration of the NMDA receptor antagonists, dizocilpine maleate (MK-801; 10 nmol rat(-1)) and D-2-amino-5-phosphono-valeric acid (AP-5; 20…
Adrenoceptor-mediated changes of excitation and contraction in isolated heart muscle preparations.
1989
The inotropic effects of sympathetic stimulation on the heart are mainly ascribed to the activation of beta-adrenoceptors. However, several findings suggest that alpha-adrenoceptors also may help mediate the inotropic response to catecholamines under certain conditions. The onset of the positive inotropic effect mediated by beta-adrenoceptors occurs within seconds and is associated with a faster rate of relaxation. Both beta 1- and beta 2-adrenoceptors are stimulatorily coupled to the enzyme adenylate cyclase, thereby leading to the generation of cyclic AMP. Cyclic AMP increases the slow inward calcium current and enhances the uptake of calcium into the sarcoplasmic reticulum. GTP-binding p…
Tachykinergic neurotransmission is enhanced in duodenum from dystrophic (mdx ) mice
2005
1 Duodenal longitudinal muscle of mdx mice, an animal model for Duchenne muscular dystrophy, showed a decrease in the electrically evoked nonadrenergic, noncholinergic (NANC) inhibitory responses associated with a reduction of the participation of nitric oxide (NO). In this study, we investigated whether the impairment of NO could also lead to alterations in the NANC excitatory transmission. 2 Nerve-evoked responses consisted of an inhibitory phase followed, at the end of stimulation, by an excitatory response characterised by an increase in amplitude of the spontaneous contractions. In mdx mice, the amplitude of the nerve-evoked contractions was significantly higher than in normals. 3 N(om…
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…