Nitric oxide induces [Ca2+]i oscillations in pituitary GH3 cells: involvement of IDR and ERG K+ currents

2006 ◽  
Vol 290 (1) ◽  
pp. C233-C243 ◽  
Author(s):  
Agnese Secondo ◽  
Anna Pannaccione ◽  
Mauro Cataldi ◽  
Rossana Sirabella ◽  
Luigi Formisano ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect ◽  
Receptor Blocker ◽  
Gh3 Cells ◽  
No Donors ◽  
Quiescent Cells ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Trisphosphate Receptor

The role of nitric oxide (NO) in the occurrence of intracellular Ca2+ concentration ([Ca2+]i) oscillations in pituitary GH3 cells was evaluated by studying the effect of increasing or decreasing endogenous NO synthesis with l-arginine and nitro-l-arginine methyl ester (l-NAME), respectively. When NO synthesis was blocked with l-NAME (1 mM) [Ca2+]i, oscillations disappeared in 68% of spontaneously active cells, whereas 41% of the quiescent cells showed [Ca2+]i oscillations in response to the NO synthase (NOS) substrate l-arginine (10 mM). This effect was reproduced by the NO donors NOC-18 and S-nitroso- N-acetylpenicillamine (SNAP). NOC-18 was ineffective in the presence of the L-type voltage-dependent Ca2+ channels (VDCC) blocker nimodipine (1 μM) or in Ca2+-free medium. Conversely, its effect was preserved when Ca2+ release from intracellular Ca2+ stores was inhibited either with the ryanodine-receptor blocker ryanodine (500 μM) or with the inositol 1,4,5-trisphosphate receptor blocker xestospongin C (3 μM). These results suggest that NO induces the appearance of [Ca2+]i oscillations by determining Ca2+ influx. Patch-clamp experiments excluded that NO acted directly on VDCC but suggested that NO determined membrane depolarization because of the inhibition of voltage-gated K+ channels. NOC-18 and SNAP caused a decrease in the amplitude of slow-inactivating ( IDR) and ether-à-go-go-related gene ( ERG) hyperpolarization-evoked, deactivating K+ currents. Similar results were obtained when GH3 cells were treated with l-arginine. The present study suggests that in GH3 cells, endogenous NO plays a permissive role for the occurrence of spontaneous [Ca2+]i oscillations through an inhibitory effect on IDR and on IERG.

Characterizing voltage-dependent Ca2+ channels coupled to VIP release and NO synthesis in enteric synaptosomes

2002 ◽  
Vol 283 (5) ◽  
pp. G1027-G1034 ◽  
Author(s):  
M. Kurjak ◽  
A. Sennefelder ◽  
M. Aigner ◽  
V. Schusdziarra ◽  
H. D. Allescher
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Channel Blockers ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
P Type ◽  
Ca2 Channels

In enteric synaptosomes of the rat, the role of voltage-dependent Ca2+channels in K+-induced VIP release and nitric oxide (NO) synthesis was investigated. Basal VIP release was 39 ± 4 pg/mg, and cofactor-substituted NO synthase activity was 7.0 ± 0.8 fmol · mg−1 · min−1. K+ depolarization (65 mM) stimulated VIP release Ca2+ dependently (basal, 100%; K+, 172.2 ± 16.2%; P < 0.05, n = 5). K+-stimulated VIP release was reduced by blockers of the P-type (ω-agatoxin-IVA, 3 × 10−8 M) and N-type (ω-conotoxin-GVIA, 10−6 M) Ca2+ channels by ∼50 and 25%, respectively, but not by blockers of the L-type (isradipine, 10−8 M), Q-type (ω-conotoxin-MVIIC, 10−6 M), or T-type (Ni2+, 10−6 M) Ca2+ channels. In contrast, NO synthesis was suppressed by ω-agatoxin-IVA, ω-conotoxin-GVIA, and isradipine by ∼79, 70, and 70%, respectively, whereas Ni2+ and ω-conotoxin-MVIIC had no effect. These findings are suggestive of a coupling of depolarization-induced VIP release primarily to the P- and N-type Ca2+ channels, whereas NO synthesis is presumably dependent on Ca2+ influx not only via the P- and N- but also via the L-type Ca2+ channel. In contrast, none of the Ca2+ channel blockers affected VIP release evoked by exogenous NO, suggesting that NO induces VIP secretion by a different mechanism, presumably involving intracellular Ca2+ stores.

scholarly journals Nitric oxide reduces energy supply by direct action on the respiratory chain in isolated cardiomyocytes

2001 ◽  
Vol 280 (5) ◽  
pp. H2350-H2356 ◽  
Author(s):  
Thomas Stumpe ◽  
Ulrich K. M. Decking ◽  
Jürgen Schrader
Keyword(s):  
Nitric Oxide ◽  
Respiratory Chain ◽  
Direct Action ◽  
Inhibitory Effect ◽  
Energy Status ◽  
Isolated Cardiomyocytes ◽  
No Donor ◽  
Quiescent Cells ◽  
Intracellular Ca ◽  
Dose Dependent

To investigate the effect of nitric oxide (NO) on cardiac energy metabolism, isolated cardiomyocytes of Wistar rats were incubated in an Oxystat system at a constant ambient Po 2 (25 mmHg) and oxygen consumption (V˙o 2); free intracellular Ca2+ (fura 2), free cytosolic adenosine [ S-adenosylhomocysteine (SAH) method], and mitochondrial NADH (autofluorescence) were measured after application of the NO donor morpholinosydnonimine (SIN-1). In Na+-free medium (contracting cardiomyocytes), V˙o 2increased from 7.9 ± 1.2 to 26.4 ± 3.1 nmol · min−1 · mg protein−1. SIN-1 (100 μmol/l) decreased V˙o 2 in contracting (−21 ± 3%) and in quiescent cells (−24 ± 7%) by the same extent. Inhibition ofV˙o 2 was dose dependent (EC50: 10−7 mol/l). S-nitroso- N-acetyl-penicillamine, another NO donor, also inhibited V˙o 2, whereas SIN-1C (100 μmol/l), the degradation product of SIN-1, displayed no inhibitory effect. Intracellular Ca2+ remained unchanged, and inhibition of protein kinases G, A, or C did not antagonize the effect of NO. Mitochondrial NADH increased with NO, indicating a reduced flux through the respiratory chain. In quiescent but not in contracting cardiomyocytes, NO significantly increased adenosine, indicating a reduced energy status. These data suggest the following. 1) NO decreases cardiac respiration, most likely via direct inhibition of the respiratory chain. 2) Whereas in quiescent cardiomyocytes the inhibition of aerobic ATP formation by NO causes reduction in energy status, contracting cells are able to compensate for the NO-induced inhibition of oxidative phosphorylation, maintaining energy status constant.

Nitric Oxide and Immune Responses in Cancer: Searching for New Therapeutic Strategies

2021 ◽  
Vol 28 ◽  
Author(s):  
Adeleh Sahebnasagh ◽  
Fatemeh Saghafi ◽  
Sina Negintaji ◽  
Tingyan Hu ◽  
Mojtaba Shabani-Boroujeni ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Cochrane Library ◽  
Signaling Molecule ◽  
No Donors ◽  
The Cochrane Library ◽  
Oxide Synthase

: In recent years, there has been an increasing interest in understanding the mysterious functions of nitric oxide (NO) and how this pleiotropic signaling molecule contributes to tumorigenesis. This review attempts to expose and discuss the information available on the immunomodulatory role of NO in cancer and recent approaches to the role of NO donors in the area of immunotherapy. To address the goal, the following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane Library, Pubmed, Medline, EMBASE from 1980 through March 2020. Valuable attempts have been made to develop distinctive NO-based cancer therapy. Although the data do not allow generalization, the evidence seems to indicate that low / moderate levels may favor tumorigenesis while higher levels would exert anti-tumor effects. In this sense, the use of NO donors could have an important therapeutic potential within immunotherapy, although there are still no clinical trials. The emerging understanding of NO-regulated immune responses in cancer may help unravel the recent features of this “double-edged sword” in cancer physiological and pathologic processes and its potential use as a therapeutic agent for cancer treatment. In short, in this review, we discuss the complex cellular mechanism in which NO, as a pleiotropic signaling molecule, participates in cancer pathophysiology. We also debate the dual role of NO in cancer and tumor progression, and clinical approaches for inducible nitric oxide synthase (iNOS) based therapy against cancer.

Role of cyclic ADP-ribose in the regulation of [Ca2+]i in porcine tracheal smooth muscle

1998 ◽  
Vol 274 (6) ◽  
pp. C1653-C1660 ◽  
Author(s):  
Y. S. Prakash ◽  
Mathur S. Kannan ◽  
Timothy F. Walseth ◽  
Gary C. Sieck
Keyword(s):  
Smooth Muscle ◽  
Second Messenger ◽  
Ruthenium Red ◽  
Tracheal Smooth Muscle ◽  
Cyclic Adp Ribose ◽  
Intracellular Ca ◽  
Subsequent Exposure ◽  
Trisphosphate Receptor ◽  
Dose Dependent Increase

The purpose of the present study was to determine whether cyclic ADP-ribose (cADPR) acts as a second messenger for Ca2+ release through ryanodine receptor (RyR) channels in tracheal smooth muscle (TSM). Freshly dissociated porcine TSM cells were permeabilized with β-escin, and real-time confocal microscopy was used to examine changes in intracellular Ca2+ concentration ([Ca2+]i). cADPR (10 nM–10 μM) induced a dose-dependent increase in [Ca2+]i, which was blocked by the cADPR receptor antagonist 8-amino-cADPR (20 μM) and by the RyR blockers ruthenium red (10 μM) and ryanodine (10 μM), but not by the inositol 1,4,5-trisphosphate receptor blocker heparin (0.5 mg/ml). During steady-state [Ca2+]ioscillations induced by acetylcholine (ACh), addition of 100 nM and 1 μM cADPR increased oscillation frequency and decreased peak-to-trough amplitude. ACh-induced [Ca2+]ioscillations were blocked by 8-amino-cADPR; however, 8-amino-cADPR did not block the [Ca2+]iresponse to a subsequent exposure to caffeine. These results indicate that cADPR acts as a second messenger for Ca2+ release through RyR channels in TSM cells and may be necessary for initiating ACh-induced [Ca2+]ioscillations.

Sources and implications of basal nitric oxide in spontaneous contractions of guinea pig taenia caeci

2003 ◽  
Vol 285 (4) ◽  
pp. G747-G753 ◽  
Author(s):  
Catalina Caballero-Alomar ◽  
Carmen Santos ◽  
Diego Lopez ◽  
M. Teresa Mitjavila ◽  
Pere Puig-Parellada
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Inhibitory Effect ◽  
No Production ◽  
Paramagnetic Resonance ◽  
Synthase Inhibitor ◽  
Spontaneous Contractions ◽  
Electron Paramagnetic

We examined in vitro the source and role of basal nitric oxide (NO) in proximal segments of guinea pig taenia caeci in nonadrenergic, noncholinergic (NANC) conditions. Using electron paramagnetic resonance (EPR), we measured the effect of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 10–4 M), the neuronal blocker tetrodotoxin (TTX, 10–6 M), or both on spontaneous contractions and on the production of basal NO. Both l-NAME and TTX, when tested alone, increased the amplitude and frequency of contractions. NO production was abolished by l-NAME and was inhibited by 38% by TTX. When tested together, l-NAME in the presence of TTX or TTX in the presence of l-NAME had no further effect on the amplitude or frequency of spontaneous contractions, and the NO production was inhibited. These findings suggest that basal NO consists of TTX-sensitive and TTX-resistant components. The TTX-sensitive NO has an inhibitory effect on spontaneous contractions; the role of TTX-resistant NO is unknown.

Role of S-Nitrosation of Cysteine Residues in Long-Lasting Inhibitory Effect of Nitric Oxide on Arterial Tone

2003 ◽  
Vol 63 (5) ◽  
pp. 1148-1158 ◽  
Author(s):  
Jacicarlos L. Alencar ◽  
Irina Lobysheva ◽  
Michel Geffard ◽  
Mamadou Sarr ◽  
Christa Schott ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect ◽  
Cysteine Residues ◽  
Arterial Tone

scholarly journals Senescence and Cancer: Role of Nitric Oxide (NO) in SASP

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1145
Author(s):  
Nesrine Mabrouk ◽  
Silvia Ghione ◽  
Véronique Laurens ◽  
Stéphanie Plenchette ◽  
Ali Bettaieb ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cancer Treatment ◽  
Cellular Senescence ◽  
Negative Effects ◽  
No Donors ◽  
Cell State ◽  
Age Related ◽  
A Cell ◽  
Secretory Phenotype

Cellular senescence is a cell state involved in both physiological and pathological processes such as age-related diseases and cancer. While the mechanism of senescence is now well known, its role in tumorigenesis still remains very controversial. The positive and negative effects of senescence on tumorigenesis depend largely on the diversity of the senescent phenotypes and, more precisely, on the senescence-associated secretory phenotype (SASP). In this review, we discuss the modulatory effect of nitric oxide (NO) in SASP and the possible benefits of the use of NO donors or iNOS inducers in combination with senotherapy in cancer treatment.

scholarly journals Cross talk between polysulfide and nitric oxide in rat peritoneal mast cells

2016 ◽  
Vol 310 (11) ◽  
pp. C894-C902 ◽  
Author(s):  
Amira Moustafa ◽  
Yoshiaki Habara
Keyword(s):  
Nitric Oxide ◽  
Mast Cells ◽  
Ryanodine Receptor ◽  
Cross Talk ◽  
Receptor Blocker ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Peritoneal Mast Cells ◽  
Intracellular Ca ◽  
Rat Peritoneal Mast Cells

The aim of this study was to define the effects of polysulfide on intracellular Ca2+ concentration ([Ca2+]i) and the underlying machinery, especially from the hydrogen sulfide (H2S) and nitric oxide (NO) perspectives, in rat peritoneal mast cells. We found that a polysulfide donor, Na2S4, increased [Ca2+]i, which is both extracellular and intracellular Ca2+ dependent. Intracellular Ca2+ release induced by Na2S4 was attenuated by the addition of a ryanodine receptor blocker. A slow-releasing H2S donor, GYY4137, dose dependently increased [Ca2+]i that was independent from extracellular Ca2+ influx. The GYY4137-induced [Ca2+]i release was partially attenuated in the presence of the ryanodine receptor blocker. Both polysulfide and H2S donors increased the intracellular NO levels in DAF-2-loaded mast cells, which were abolished by an NO scavenger, cPTIO. Inhibition of NO synthase (NOS) significantly abolished the polysulfide- or H2S-donor-induced [Ca2+]i elevation in the absence of extracellular Ca2+. An NO donor, diethylamine (DEA) NONOate, increased [Ca2+]i in a concentration-dependent manner, in which both extracellular and intracellular Ca2+ are associated. At higher concentrations, the DEA NONOate-induced [Ca2+]i increases were attenuated in the absence of extracellular Ca2+ and by the addition of the ryanodine receptor blocker. H2S and NO dose dependently induced polysulfide production. Curiously, polysulfide, H2S, and NO donors had no effect on mast cell degranulation. Among synthases, cystathionine-γ-lyase, and neuronal NOS seemed to be the major H2S- and NO-producing synthases, respectively. These results indicate that polysulfide acts as a potential signaling molecule that regulates [Ca2+]i homeostasis in rat peritoneal mast cells via a cross talk with NO and H2S.

scholarly journals Epac activation inhibits IL-6-induced cardiac myocyte dysfunction

2016 ◽  
Vol 68 (1) ◽  
pp. 77-87 ◽  
Author(s):  
Huiling Jin ◽  
Takayuki Fujita ◽  
Meihua Jin ◽  
Reiko Kurotani ◽  
Yuko Hidaka ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Cardiac Myocyte ◽  
Cardiac Contractility ◽  
Inhibitory Effect ◽  
Intracellular Ca ◽  
Dependent Protein ◽  
Novel Target ◽  
Oxide Synthase ◽  
Stat Pathway

Abstract Pro-inflammatory cytokines are released in septic shock and impair cardiac function via the Jak-STAT pathway. It is well known that sympathetic and thus catecholamine signaling is activated thereafter to compensate for cardiac dysfunction. The mechanism of such compensation by catecholamine signaling has been traditionally understood to be cyclic AMP-dependent protein kinase (PKA)-mediated enforcement of cardiac contractility. We hypothesized that the exchange protein activated by cAMP (Epac), a newly identified target of cAMP signaling that functions independently of PKA, also plays a key role in this mechanism. In cultured cardiac myocytes, activation of Epac attenuated the inhibitory effect of interleukin-6 on the increase of intracellular Ca2+ concentration and contractility in response to isoproterenol, most likely through inhibition of the Jak-STAT pathway via SOCS3, with subsequent changes in inducible nitric oxide synthase expression. These findings suggest a new role of catecholamine signaling in compensating for cardiac dysfunction in heart failure. Epac and its downstream pathway may be a novel target for treating cardiac dysfunction in endotoxemia.

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