Search results for "Cyclase"
showing 10 items of 141 documents
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…
Adrenergic Stimulation of Cyclic GMP Formation Requires NO-Dependent Activation of Cytosolic Guanylate Cyclase in Rat Pinealocytes
1993
Cyclic GMP (cGMP) formation in rat pinealocytes is regulated through a synergistic dual receptor mechanism involving beta- and alpha 1-adrenergic receptors. The effects of NG-monomethyl-L-arginine (NMMA), which inhibits nitric oxide (NO) synthase and NO-mediated activation of cytosolic guanylate cyclase, and methylene blue (MB), which inhibits cytosolic guanylate cyclase, were investigated in an attempt to understand the role of NO in adrenergic cGMP formation. Both NMMA and MB inhibited beta-adrenergic stimulation of cGMP formation as well as alpha 1-adrenergic potentiation of beta-adrenergic stimulation of cGMP formation, whereas they had no effect in unstimulated pinealocytes. The inhibi…
Stabilization of Perivascular Mast Cells by Endothelial CNP (C-Type Natriuretic Peptide)
2020
Objective: Activated perivascular mast cells (MCs) participate in different cardiovascular diseases. Many factors provoking MC degranulation have been described, while physiological counterregulators are barely known. Endothelial CNP (C-type natriuretic peptide) participates in the maintenance of vascular barrier integrity, but the target cells and mechanisms are unclear. Here, we studied whether MCs are regulated by CNP. Approach and Results: In cultured human and murine MCs, CNP activated its specific GC (guanylyl cyclase)-B receptor and cyclic GMP signaling. This enhanced cyclic GMP–dependent phosphorylation of the cytoskeleton-associated VASP (vasodilator-stimulated phosphoprotein) and…
NADPH Oxidase Accounts for Enhanced Superoxide Production and Impaired Endothelium-Dependent Smooth Muscle Relaxation in BKβ1 −/− Mice
2006
Objective— Nitric oxide (NO)-induced vasorelaxation involves activation of large conductance Ca 2+ -activated K + channels (BK). A regulatory BKβ1 subunit confers Ca 2+ , voltage, and NO/cGMP sensitivity to the BK channel. We investigated whether endothelial function and NO/cGMP signaling is affected by a deletion of the β1-subunit. Methods and Results— Vascular superoxide in BKβ1 −/− was measured using the fluorescent dye hydroethidine and lucigenin-enhanced chemiluminescence. Vascular NO formation was analyzed using electron paramagnetic resonance (EPR), expression of NADPH oxidase subunits, the endothelial NO synthase (eNOS), the soluble guanylyl cyclase (sGC), as well as the activity a…
Histamine-sensitive adenylate cyclase of human gastric mucosa: a model for H2-receptor excitation.
1978
Recent studies revealed that human gastric mucosa contains a histamine-sensitive adenylate cyclase which is almost completely localized within the acid-secreting area of the stomach. In an attempt to further characterize the effector system of histamine’s action, we compared the effects of H 1 — and H 2-receptor agonists upon the adenylate cyclase in human fundic gastric mucosa.
Repression of Cyclic Adenosine Monophosphate Upregulation Disarms and Expands Human Regulatory T Cells
2011
Abstract The main molecular mechanism of human regulatory T cell (Treg)-mediated suppression has not been elucidated. We show in this study that cAMP represents a key regulator of human Treg function. Repression of cAMP production by inhibition of adenylate cyclase activity or augmentation of cAMP degradation through ectopic expression of a cAMP-degrading phosphodiesterase greatly reduces the suppressive activity of human Treg in vitro and in a humanized mouse model in vivo. Notably, cAMP repression additionally abrogates the anergic state of human Treg, accompanied by nuclear translocation of NFATc1 and induction of its short isoform NFATc1/αA. Treg expanded under cAMP repression, however,…
Effects of sodium fluoride on the mechanical activity in mouse gastric preparations.
2005
The aim of the present study was to investigate the responses induced by sodium fluoride (NaF) on gastric mechanical activity, using mouse whole-stomach preparations. The mechanical activity was recorded in vitro as changes of intraluminal pressure. In most of the preparations, NaF induced a tetrodotoxin-insensitive biphasic effect characterized by early relaxation followed by slowly developing contractile response. The contraction was dependent on the concentration of NaF, whereas the relaxation was observed at only 10–30 mmol/L NaF. The contractile effect was significantly reduced by nifedipine (an L-type Ca2+channel blocker), ryanodine or ruthenium red (inhibitors of Ca2+release from sar…
Modulation by docosahexaenoic acid of the epinephrine-stimulated adenylate cyclase activity of the bovine retina.
1988
This work shows that unsaturated fatty acids enhance the epinephrine-stimulated adenylate cyclase activity in bovine retina. The modulating effect on the epinephrine-stimulated formation of cyclic AMP seems to be linked to the degree of unsaturation of the fatty acid. Treatment of the intact retina with docosahexaenoic acid in the concentration range 0.5 X 10(-6)-1 X 10(-3) M does not affect the enzyme activity measured in the absence of the hormone but markedly increases the cyclase activity when the tissue is incubated in the presence of 0.1 mM epinephrine. Docosahexaenoic acid enhances the maximal response to epinephrine without affecting the apparent ED50 value for this effector. Docosa…
Role of the cyclic AMP-dependent pathway in free radical-induced cholesterol accumulation in vascular smooth muscle cells.
2000
We have previously reported that free radical-treated vascular smooth muscle cells (SMC) lead to cholesterol accumulation in vitro. In the current study, we investigated the effects of oxidative stress on cyclic AMP concentration and cAMP-dependent enzymes involved in cholesterol homeostasis in A7r5 cells. Under our conditions of a mild oxidative stress, namely with no change in cell viability, we found that free radicals, initiated using azobis-amidinopropane dihydrochloride (AAPH), resulted in a dose-dependent decrease in cellular cAMP which was opposed by vitamin E preincubation. Although the addition of adenylate cyclase activators (carbacyclin and forskolin) increased cAMP levels it di…
Vasoactive intestinal peptide stimulation of cyclic guanosine monophosphate formation: further evidence for a role of nitric oxide synthase and cytos…
1993
In the rat pineal gland vasoactive intestinal peptide (VIP) and beta-adrenergic agonists stimulate cyclic guanosine monophosphate (cGMP) formation and their action is amplified by alpha 1-adrenergic agonists. Since beta-adrenergic stimulation of cGMP is suggested to involve activation of nitric oxide (NO) synthase and NO-mediated activation of cytosolic guanylate cyclase (GC), we investigated the effects of the NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA) and of the cytosolic GC inhibitor methylene blue (MB) on VIP receptor-stimulated cGMP formation. Both L-NMMA and MB depressed VIP-induced cGMP formation as well as alpha 1-adrenergic potentiation of VIP-stimulated cGMP formation …