Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase

Bredt, David S.; Glatt, Charles E.; Hwang, Paul M.; Fotuhi, Majid; Dawson, Ted M.; Snyder, Solomon H.

doi:10.1016/0896-6273(91)90374-9

Cited by 1,306 publications

(529 citation statements)

References 25 publications

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“…Actually localization of calmodulin-dependent adenylyl cyclase in the brain are quite similar to that of IRK2 mRNA [17]. The distributions of mRNAs of nitric oxide synthase [18] and IRK1 are also very similar in the brain. These suggest that IRKs can be regulated by various second messengers and may play important roles in regulation of neural excitability.…”

Section: Discussionmentioning

confidence: 62%

Differential distribution of classical inwardly rectifying potassium channel mRNAs in the brain: comparison of IRK2 with IRK1 and IRK3

et al. 1996

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Distribution of IRK2 inwardly rectifying potassium channel mRNA in the mouse brain was studied using in situ hybridization histochemistry and compared with those of other classical inwardly rectifying potassium channel (IRK1 and IRK3) mRNAs. All these IRK channel mRNAs were detected in neurons, but not in glial cells. Their distribution patterns in the brain were, however, quite divergent: IRK2 mRNA was detected extremely high in granule cells of cerebellum, relatively high in motor trigeminai nucleus and moderate in olfactory bulb, piriform cortex, cerebral cortex, CA1 through CA3 regions of hippocampus, dentate gyrus and pontine nucleus. On the other hand, IRK1 mRNA was expressed throughout whole brain but in particular subsets of neurons, and IRK3 mRNA was in forebrain. Expression of these three IRK mRNAs overlapped in hippocampus, olfactory bulb, and cerebral cortex. This differential distribution of IRK mRNAs suggests that each of these channels has its specific function in regulation of the excitability of brain neurons.

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Section: Discussionmentioning

confidence: 62%

Differential distribution of classical inwardly rectifying potassium channel mRNAs in the brain: comparison of IRK2 with IRK1 and IRK3

et al. 1996

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“…Despite these findings, however, our studies do not support the postulate that cGMP is involved in the signal-transduction mechanism of NO's action on magnocellular neuroendocrine neurons. This was demonstrated by the following findings from our laboratory (10): 1) basal plasma concentrations of vasopressin and oxytocin do not become elevated when sGC activity is inhibited with 1H- [1,2,4]oxadiazolo- [4,3-a] quinoxalin-1-one (ODQ) administered icv to conscious rats; 2) administration of a membrane-permeable analog of cGMP (8-BrcGMP; icv) to conscious dehydrated rats does not modify plasma hormone levels; 3) activity of NOS increases significantly in homogenates of the pituitary neural lobe of rats drinking 2% NaCl as the sole source of fluids for 4 days without any change in sGC activity or production of cGMP, and 4) the activity of NOS increases in microdialysates of the SON during osmotic stimulation in conscious and pentobarbital-anesthetized rats without changes in cGMP production.…”

Section: No and Signal-transduction Pathwaymentioning

confidence: 82%

Nitric oxide modulation of the hypothalamo-neurohypophyseal system

Kadekaro

2004

Braz J Med Biol Res

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Nitric oxide (NO), a free radical gas produced endogenously from the amino acid L-arginine by NO synthase (NOS), has important functions in modulating vasopressin and oxytocin secretion from the hypothalamo-neurohypophyseal system. NO production is stimulated during increased functional activity of magnocellular neurons, in parallel with plastic changes of the supraoptic nucleus (SON) and paraventricular nucleus. Electrophysiological data recorded from the SON of hypothalamic slices indicate that NO inhibits firing of phasic and non-phasic neurons, while L-NAME, an NOS inhibitor, increases their activity. Results from measurement of neurohypophyseal hormones are more variable. Overall, however, it appears that NO, tonically produced in the forebrain, inhibits vasopressin and oxytocin secretion during normovolemic, isosmotic conditions. During osmotic stimulation, dehydration, hypovolemia and hemorrhage, as well as high plasma levels of angiotensin II, NO inhibition of vasopressin neurons is removed, while that of oxytocin neurons is enhanced. This produces a preferential release of vasopressin over oxytocin important for correction of fluid imbalance. During late pregnancy and throughout lactation, fluid homeostasis is altered and expression of NOS in the SON is down-and up-regulated, respectively, in parallel with plastic changes of the magnocellular system. NO inhibition of magnocellular neurons involves GABA and prostaglandin synthesis and the signal-transduction mechanism is independent of the cGMP-pathway. Plasma hormone levels are unaffected by icv 1H-[1, 2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor) or 8-Br-cGMP administered to conscious rats. Moreover, cGMP does not increase in homogenates of the neural lobe and in microdialysates of the SON when NO synthesis is enhanced during osmotic stimulation. Among alternative signal-transduction pathways, nitrosylation of target proteins affecting activity of ion channels is considered.

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“…Endothelial NOS is located on the cell membrane and releases NO for short periods of time in response to receptor or physical stimulation. Neuronal NOS has been identified in the cytosol of central and peripheral neurons [7]. The inducible form of NOS (iNOS), which is Ca 2+ -independent, can be found in inflammatory cells, such as macrophages, after they are activated by proinflammatory mediators like oxidants, cytokines and endotoxins.…”

mentioning

confidence: 99%

Inhibition of nitric oxide synthase by nasal decongestants

Westerveld¹,

Voss²,

Hee³

et al. 2000

Eur Respir J

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The nasal decongestants oxymetazoline and xylometazoline are frequently used in the topical treatment of rhinitis and sinusitis. As nitric oxide (NO) is thought to play a role in inflammation of the upper respiratory tract, the aim of this study was to examine the in vitro effects of these compounds on the activity and the expression of NO producing enzymes, including the inducible form of NO synthase (iNOS) and the constitutive isoform of NO synthase (cNOS).Experiments concerning the effects of both compounds on enzymatic activity and enzyme induction of iNOS were performed in a lipopolysaccharide (LPS) induced rat alveolar macrophage cell line (NR8383) using the Griess assay and the 3 H-citrulline assay respectively. The effects on cNOS were examined in fresh rat synaptosomes using the 3 H-citrulline assay. The direct scavenging properties of both compounds were investigated using a amperometric NO sensor.Oxymetazoline and xylometazoline were shown to have a dose dependent inhibitory effect on total iNOS activity indicated by nitrite/nitrate formation in the Griess assay. This effect was found to be due to an inhibition of induction of the enzyme rather than inhibition of the enzyme activity, as was investigated in two separate experiments using the 3 H-citrulline assay. Inhibition of cNOS was moderate and in the same order of magnitude as the inhibition of enzymatic iNOS activity. Direct scavenging of NO could not be detected.As constitutive nitric oxide synthase activity is thought to serve beneficial physiological functions, and exaggerated inducible nitric oxide synthase activity may cause exacerbation of the inflammatory process, pharmacological treatment influencing the nitric oxide generating system should focus on inhibition of inducible nitric oxide synthase alone. The specific characteristics of these decongestants in vitro suggests suitability for this application and may indicate an additional beneficial effect in the treatment of upper respiratory tract inflammation. Eur Respir J 2000; 16: 437±444.

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Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase

Cited by 1,306 publications

References 25 publications

Differential distribution of classical inwardly rectifying potassium channel mRNAs in the brain: comparison of IRK2 with IRK1 and IRK3

Differential distribution of classical inwardly rectifying potassium channel mRNAs in the brain: comparison of IRK2 with IRK1 and IRK3

Nitric oxide modulation of the hypothalamo-neurohypophyseal system

Inhibition of nitric oxide synthase by nasal decongestants

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