Effects of L-arginine-derived nitric oxide synthesis on neuronal activity in nucleus tractus solitarius

1995 ◽  
Vol 268 (2) ◽  
pp. R487-R491 ◽  
Author(s):  
S. Ma ◽  
F. M. Abboud ◽  
R. B. Felder
Keyword(s):  
Nitric Oxide ◽  
Neuronal Activity ◽  
Nucleus Tractus Solitarius ◽  
Discharge Rate ◽  
Brain Slices ◽  
Spontaneous Discharge ◽  
Fischer 344 Rats ◽  
Fischer 344

The purpose of these studies was to determine the effects of L-arginine-derived nitric oxide (NO) synthesis on neuronal activity in solitary tract nucleus (NTS) neurons. Single unit activity was recorded extracellularly from medial NTS neurons in Fischer-344 rats in vivo and in vitro. In anesthetized rats with arterial pressure maintained constant, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv), an inhibitor of NO synthesis, decreased the discharge rate in 12 of 14 neurons and increased the discharge rate in two. After injection of L-NAME, the slowing of neuronal activity began within 2-5 min, and maximal responses were observed 12-15 min after injection. The decreases in activity were reversed within 12-15 min with L-arginine (30 mg/kg iv) or immediately with nitroglycerin (NTG, 10-30 micrograms/kg iv). In superfused rat brain slices, the discharge rate was reduced by 1 mM L-NAME in seven neurons, increased in two, and unchanged in one. The decreases in discharge rate were reversed by 2 mM L-arginine (4 of 6 neurons) and by 10-30 microM NTG (6 of 7 neurons). The results show that L-arginine-derived NO can affect the spontaneous discharge rate of NTS neurons. We conclude that NO may influence the excitability of NTS neurons involved in central autonomic control.

scholarly journals Local Opiate Withdrawal in Locus Coeruleus Neurons In Vitro

2001 ◽  
Vol 85 (6) ◽  
pp. 2388-2397 ◽  
Author(s):  
Alexander Ivanov ◽  
Gary Aston-Jones
Keyword(s):  
Protein Kinase ◽  
Locus Coeruleus ◽  
Protein Kinase A ◽  
Discharge Rate ◽  
Brain Slices ◽  
Opiate Withdrawal ◽  
Spontaneous Discharge ◽  
Chronic Morphine ◽  
Kinase A

Noradrenergic neurons of the brain nucleus locus coeruleus (LC) become hyperactive during opiate withdrawal. It has been uncertain to what extent such hyperactivity reflects changes in intrinsic properties of these cells. The effects of withdrawal from chronic morphine on the activity of LC neurons were studied using intracellular recordings in rat brain slices. LC neurons in slices from chronically morphine-treated rats exhibited more than twice the frequency of spontaneous action potentials after naloxone compared with LC neurons from control rats. However, after naloxone treatment, the resting membrane potential (MP) of LC neurons from dependent rats was not significantly different from that in control rats. Neither resting MP nor spontaneous discharge rate (SDR) was altered by naloxone in LC neurons from control rats. Neither kynurenic acid nor a cocktail of glutamate and GABA antagonists (6-cyano-7-nitroquinoxalene-2,3-dione + 2-amino-5-phosphonopentanoic acid + bicuculline) blocked the hyperactivity of LC neurons precipitated by naloxone in slices from morphine-dependent rats. The effects of ouabain on MP and SDR were similar in LC neurons from control and morphine-dependent rats. These results indicate that an adaptive change in glutamatergic or GABAergic synaptic mechanisms or altered Na/K pump activity does not underlie the withdrawal-induced activation of LC neurons in vitro. Specific inhibitors of protein kinase A [Rp-cAMPS or N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H-89)] partially suppressed the withdrawal hyperactivity of LC neurons, and activators of cAMP (forskolin) or protein kinase A (Sp-cAMPS) increased the discharge rate of LC neurons from control rats. These results suggest that upregulation of cAMP-dependent protein kinase A during chronic morphine treatment is involved in the withdrawal-induced hyperactivity of LC neurons.

Rhythmic multiunit neural activity in slices of hamster suprachiasmatic nucleus reflect prior photoperiod

2000 ◽  
Vol 278 (4) ◽  
pp. R987-R994 ◽  
Author(s):  
Maciej Mrugala ◽  
Piotr Zlomanczuk ◽  
Anita Jagota ◽  
William J. Schwartz
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Neuronal Activity ◽  
Brain Slices ◽  
Day Length ◽  
Electrophysiological Activity ◽  
Discharge Rates ◽  
Subjective Night ◽  
The Mean

The suprachiasmatic nucleus (SCN) is an endogenous circadian pacemaker, and SCN neurons exhibit circadian rhythms of electrophysiological activity in vitro. In vivo, the functional state of the pacemaker depends on changes in day length (photoperiod), but it is not known if this property persists in SCN tissue isolated in vitro. To address this issue, we prepared brain slices from hamsters previously entrained to light-dark (LD) cycles of different photoperiods and analyzed rhythms of SCN multiunit neuronal activity using single electrodes. Rhythms in SCN slices from hamsters entrained to 8:16-, 12:12-, and 14:10-h LD cycles were characterized by peak discharge rates relatively higher during subjective day than subjective night. The mean duration of high neuronal activity was photoperiod dependent, compressed in slices from the short (8:16 and 12:12 LD) photoperiods, and decompressed (approximately doubled) in slices from the long (14:10 LD) photoperiod. In slices from all photoperiods, the mean phase of onset of high neuronal activity appeared to be anchored to subjective dawn. Our results show that the electrophysiological activity of the SCN pacemaker depends on day length, extending previous in vivo data, and demonstrate that this capacity is sustained in vitro.

scholarly journals Nephrotoxic Potential of Putative 3,5-Dichloroaniline (3,5-DCA) Metabolites and Biotransformation of 3,5-DCA in Isolated Kidney Cells from Fischer 344 Rats

2020 ◽  
Vol 22 (1) ◽  
pp. 292
Author(s):  
Gary O. Rankin ◽  
Christopher R. Racine ◽  
Monica A. Valentovic ◽  
Dianne K. Anestis
Keyword(s):  
Reactive Metabolites ◽  
Kidney Cells ◽  
Fischer 344 Rats ◽  
Isolated Kidney ◽  
Renal Metabolism ◽  
Fischer 344 ◽  
Primary Mechanism ◽  
Toxic Metabolites

The current study was designed to explore the in vitro nephrotoxic potential of four 3,5-dichloroaniline (3,5-DCA) metabolites (3,5-dichloroacetanilide, 3,5-DCAA; 3,5-dichlorophenylhydroxylamine, 3,5-DCPHA; 2-amino-4,6-dichlorophenol, 2-A-4,6-DCP; 3,5-dichloronitrobenzene, 3,5-DCNB) and to determine the renal metabolism of 3,5-DCA in vitro. In cytotoxicity testing, isolated kidney cells (IKC) from male Fischer 344 rats (~4 million/mL, 3 mL) were exposed to a metabolite (0–1.5 mM; up to 90 min) or vehicle. Of these metabolites, 3,5-DCPHA was the most potent nephrotoxicant, with 3,5-DCNB intermediate in nephrotoxic potential. 2-A-4,6-DCP and 3,5-DCAA were not cytotoxic. In separate experiments, 3,5-DCNB cytotoxicity was reduced by pretreating IKC with antioxidants and cytochrome P450, flavin monooxygenase and peroxidase inhibitors, while 3,5-DCPHA cytotoxicity was attenuated by two nucleophilic antioxidants (glutathione and N-acetyl-L-cysteine). Incubation of IKC with 3,5-DCA (0.5–1.0 mM, 90 min) produced only 3,5-DCAA and 3,5-DCNB as detectable metabolites. These data suggest that 3,5-DCNB and 3,5-DCPHA are potential nephrotoxic metabolites and may contribute to 3,5-DCA induced nephrotoxicity in vivo. In addition, the kidney can bioactivate 3,5-DCNB to toxic metabolites, and 3,5-DCPHA appears to generate reactive metabolites to contribute to 3,5-DCA nephrotoxicity. In vitro, N-oxidation of 3,5-DCA appears to be the primary mechanism of bioactivation of 3,5-DCA to nephrotoxic metabolites.

scholarly journals Ginkgolide B Maintains Calcium Homeostasis in Hypoxic Hippocampal Neurons by Inhibiting Calcium Influx and Intracellular Calcium Release

2021 ◽  
Vol 14 ◽  
Author(s):  
Li Wang ◽  
Quan Lei ◽  
Shuai Zhao ◽  
WenJuan Xu ◽  
Wei Dong ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Calcium Release ◽  
Calcium Influx ◽  
Brain Slices ◽  
Spontaneous Discharge ◽  
Protective Effects ◽  
Ginkgolide B ◽  
Pre Treatment

Ginkgolide B (GB), a terpene lactone and active ingredient of Ginkgo biloba, shows protective effects in neuronal cells subjected to hypoxia. We investigated whether GB might protect neurons from hypoxic injury through regulation of neuronal Ca2+ homeostasis. Primary hippocampal neurons subjected to chemical hypoxia (0.7 mM CoCl2) in vitro exhibited an increase in cytoplasmic Ca2+ (measured from the fluorescence of fluo-4), but this effect was significantly diminished by pre-treatment with 0.4 mM GB. Electrophysiological recordings from the brain slices of rats exposed to hypoxia in vivo revealed increases in spontaneous discharge frequency, action potential frequency and calcium current magnitude, and all these effects of hypoxia were suppressed by pre-treatment with 12 mg/kg GB. Western blot analysis demonstrated that hypoxia was associated with enhanced mRNA and protein expressions of Cav1.2 (a voltage-gated Ca2+ channel), STIM1 (a regulator of store-operated Ca2+ entry) and RyR2 (isoforms of Ryanodine Receptor which mediates sarcoplasmic reticulum Ca2+ release), and these actions of hypoxia were suppressed by GB. Taken together, our in vitro and in vivo data suggest that GB might protect neurons from hypoxia, in part, by regulating Ca2+ influx and intracellular Ca2+ release to maintain Ca2+ homeostasis.

Cold- and norepinephrine-induced thermogenesis in younger and older Fischer 344 rats

1988 ◽  
Vol 254 (3) ◽  
pp. R457-R462 ◽  
Author(s):  
R. B. McDonald ◽  
B. A. Horwitz ◽  
J. S. Hamilton ◽  
J. S. Stern
Keyword(s):  
Body Mass ◽  
Mitochondrial Protein ◽  
Brown Fat ◽  
O2 Consumption ◽  
Fischer 344 Rats ◽  
Nonshivering Thermogenesis ◽  
Fischer 344 ◽  
Isolated Mitochondria

Older rats exposed to low environmental temperatures show attenuated thermogenesis. However, the mechanisms responsible for this attenuation are not clear. This investigation evaluated the possibility that reduced nonshivering thermogenic capacity is associated with this attenuation. O2 consumption was measured in male Fischer 344 rats ages 7 and 24 mo at thermoneutrality (26 degrees C), during exposure to cold (6 degrees C) for 2 h, and during norepinephrine (NE) infusion (an in vivo measure of nonshivering thermogenesis). In addition, the binding of GDP to isolated mitochondria of brown fat, an in vitro estimate of nonshivering thermogenesis, was also measured. Resting mass-independent O2 consumption (ml.min-1.g body mass -0.67) was not different between the two age groups. However, mass-independent O2 consumption was significantly greater in the younger vs. older rats during 2 h of cold exposure (younger, 2.86 +/- 0.19 l/kg body mass 0.67; older, 2.39 +/- 0.10 l/kg body mass 0.67) and during 20 min of maximum NE infusion (younger, 410.4 +/- 15.1 ml/kg body mass)] was greater in younger than ml/kg body mass 0.67). Brown fat mass [absolute (g) as well as relative (g tissue/kg body mass)] was greater in younger than in older rats. Furthermore, younger rats had significantly greater binding of GDP to isolated mitochondria of brown fat than did the older rats. This effect was true whether the data were expressed as nanomoles bound per milligram mitochondrial protein (32% lower in older rats), bound nanomoles recovered (57% lower), or bound picogram per kilogram body mass 0.67 (59% lower).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals In Vitro and In Vivo Anti-Inflammatory Effects of Sulfated Polysaccharides Isolated from the Edible Brown Seaweed, Sargassum fulvellum

Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 277
Author(s):  
Lei Wang ◽  
Hye-Won Yang ◽  
Ginnae Ahn ◽  
Xiaoting Fu ◽  
Jiachao Xu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brown Seaweed ◽  
Sulfated Polysaccharides ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Sargassum Fulvellum ◽  
Pharmaceutical Industries ◽  
Anti Inflammatory

In the present study, the in vitro and in vivo anti-inflammatory effects of the sulfated polysaccharides isolated from Sargassum fulvellum (SFPS) were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results indicated that SFPS improved the viability of LPS-stimulated RAW 264.7 macrophages from 80.02 to 86.80, 90.09, and 94.62% at the concentration of 25, 50, and 100 µg/mL, respectively. Also, SFPS remarkably and concentration-dependently decreased the production levels of inflammatory molecules including nitric oxide (NO), tumor necrosis factor-alpha, prostaglandin E2, interleukin-1 beta, and interleukin-6 in LPS-treated RAW 264.7 macrophages. In addition, SFPS significantly inhibited the expression levels of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-treated RAW 264.7 macrophages. Furthermore, the in vivo test results indicated that SFPS improved the survival rate of LPS-treated zebrafish from 53.33 to 56.67, 60.00, and 70.00% at the concentration of 25, 50, and 100 µg/mL, respectively. In addition, SFPS effectively reduced cell death, reactive oxygen species, and NO levels in LPS-stimulated zebrafish. Taken together, these results suggested that SFPS possesses strong in vitro and in vivo anti-inflammatory activities, and could be used as an ingredient to develop anti-inflammatory agents in the functional food and pharmaceutical industries.

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