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1.
Evidence is presented that nitric oxide (NO) may regulate blood pressure in cephalopod molluscs. In vitro tests performed on the cephalic aorta of Sepia officinalis (L.) (Cephalopoda) showed that the NO releasers (glyceroltrinitrate, sodium nitroprusside, 3-morpholinylsydnoneimine chloride and KNO(2)) induced concentration-dependent vasodilatation of vessel segments (without the tunica adventitia/periadventitia) precontracted by dopamine. These vasodilatatory actions could be totally blocked by oxadiazolo[4,3-a] quinoxalin-1-one, an inhibitor of the NO-sensitive guanylyl cyclase, and partially mimicked by the cyclic guanosine monophosphate (cGMP) analogue 8-bromo cGMP and by the phosphodiesterase inhibitor, zaprinast. The NO-precursor, L-arginine, showed vasodilatatory effects only on segments of the aorta in which the layers containing nerves (tunica adventitia/periadventitia) had been left intact, suggesting that NO synthase may be located within peripheral nerves. 相似文献
2.
Evidence that lithium induces a glutamatergic: Nitric oxide-mediated response in rat brain 总被引:3,自引:0,他引:3
Brian H. Harvey Machteld E. Carstens Joshua J. F. Taljaard 《Neurochemical research》1994,19(4):469-474
Studies have indicated the involvement of a glutamatergic mechanism in lithium (Li+) action. Glutamatergic agonists, such as kainic acid, are known to promote the synthesis of nitric oxide (NO) and to increase cGMP, while Li+ has displayed a similar, yet unexplained, ability to increase cGMP. NO synthesis is regarded as the principal prodromal event leading to the activation of the guanyl cyclase-cGMP transduction mechanism. In the present study, the involvement of the NO:cGMP pathway in the action of Li+ was examined, while the possibility of a glutamatergic mechanism in this response was also investigated. Parameters examined included cortical accumulation of cGMP and the stable oxidative metabolites of NO, viz. NO
2
– and NO
3
–, collectively expressed as NO
2
–. A significant positive correlation was observed in the in vivo cGMP and NO
2
– data throughout all the groups. Chronic treatment of rats with LiCl (0.3% m/m) engendered a significant increase in cGMP levels which was inhibited by the NO-synthase (NOS) inhibitor, N-nitro-l-arginine methyl ester (L-NAME). Acute administration of kainic acid resulted in an increased accumulation of NO
2
–, also prevented by concomitant L-NAME administration. In addition, a synergistic stimulatory response on cortical NO
2
– was observed in the combination of LiCl and kainic acid. Collectively, these data implicate an involvement of a glutamatergic-mediated NO:cGMP transduction mechanism in the action of Li+. 相似文献
3.
Schepelmann M Molcan L Uhrova H Zeman M Ellinger I 《Cellular and molecular neurobiology》2011,31(8):1257-1265
Melatonin is involved in blood pressure modulation in rats and humans. Some of the effects of melatonin are presumably mediated
via two G-protein-coupled receptors (MT1 and MT2), but the distribution of MT1 and MT2 in the cardiovascular system remains to be explored comprehensively. We investigated the expression of both the receptors
in the rat aorta on mRNA level by RT-PCR and real time RT-PCR as well as on protein level via western blotting and immunofluorescence
microscopy. We verified MT1 mRNA expression in the rat aorta and demonstrated the absence of MT2 mRNA in this vessel type. MT1 receptors were confirmed also at the protein level, and surprisingly they were preferentially localized to the tunica adventitia.
Since no daily changes in MT1 mRNA expression were detected, we suppose that the circadian changes in circulating melatonin concentrations are sufficient
to mediate circadian effects of melatonin in the aorta. The localization of MT1 in the tunica adventitia suggests an influence of melatonin on vasa vasorum function and signal transduction in the aorta
wall. 相似文献
4.
Modulation of GABA Release by Second Messenger Substances and NO in Mouse Brain Stem Slices Under Normal and Ischemic Conditions 总被引:1,自引:0,他引:1
GABA is the inhibitory neurotransmitter in most brain stem nuclei. The properties of release of preloaded [3H]GABA were now investigated with slices from the mouse brain stem under normal and ischemic (oxygen and glucose deprivation) conditions, using a superfusion system. The ischemic GABA release increased about fourfold in comparison with normal conditions. The tyrosine kinase inhibitor genistein had no effect on GABA release, while the phospholipase inhibitor quinacrine reduced both the basal and K+-evoked release in normoxia and ischemia. The activator of protein kinase C (PKC) 4β-phorbol 12-myristate 13-acetate had no effects on the releases, whereas the PKC inhibitor chelerythrine reduced the basal release in ischemia. When the cyclic guanosine monophosphate (cGMP) levels were increased by superfusion with zaprinast and other phosphodiesterase inhibitors, GABA release was reduced under normal conditions. The NO donors S-nitroso-N-acetylpenicillamine (SNAP) and hydroxylamine (HA) enhanced the basal and K+-stimulated release by acting directly on presynaptic terminals. Under ischemic conditions GABA release was enhanced when cGMP levels were increased by zaprinast. This effect was confirmed by inhibition of the release by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The NO-producing agents SNAP, HA, and sodium nitroprusside potentiated GABA release in ischemia. These effects were reduced by the NO synthase inhibitor NG-nitro-l-arginine, but not by ODQ. The results show that particularly NO and cGMP regulate both normal and ischemic GABA release in the brain stem. Their effects are however complex. 相似文献
5.
Hong E Larios F Gómez-Viquez NL Huang F Bravo G 《Journal of physiology and biochemistry》2011,67(3):427-435
The contribution of α-adrenoceptors and nitric oxide (NO) on the alterations of sympathetically mediated cardiovascular responses
after acute (AcH) and chronic (ChH) hypertension was evaluated in pithed aortic coarcted hypertensive rats. Pressor and tachycardia
response produced by electrical stimulation of preganglionic sympathetic fibers or exogenous noradrenaline (NA) were recorded
in the absence and presence of prazosin (α1-antagonist), rauwolscine (α2-antagonist), or N
G-nitro-l-arginine methyl ester (l-NAME; an inhibitor of NO synthase). Compared with age-matched sham-operated rats (Nt), the pressor response produced by electrical
stimulation or NA was smaller in AcH rats and larger in ChH rats. Prazosin caused a decrease of pressor response elicited
by electrical stimulation or NA in all groups. However, this effect was higher in ChH. Rauwolscine produced a similar increase
of sympathetically mediated pressor response in Nt and AcH rats. Nevertheless, this antagonist did not affect the sympathetically
mediated pressor response in ChH rats. In addition, rauwolscine did not affect the NA-induced pressor response in all groups.
The pressor response elicited by l-NAME was larger in all groups compared without l-NAME and in presence of l-arginine. Moreover, l-NAME in the presence of NA increased sympathetically mediated pressor response is in all groups, compared without it or in
the presence of l-arginine. Compared with Nt, basally produced NO in aortic rings was increased in AcH but decreased in ChH. Collectively,
our data suggest that decreased cardiovascular reactivity in AcH is due to an increase in basally produced NO. In ChH, enhanced
cardiovascular response appears to be associated with a decrease in produced NO and an increase in released NA from sympathetic
nerves. 相似文献
6.
《Life sciences》1994,54(9):PL153-PL158
Thapsigargin induced endothelium-dependent relaxation and cGMP production in rat thoracic aorta, and these effects were inhibited by nitric oxide (NO) pathway inhibitors, a calmodulin inhibitor and removal of Ca2+, suggesting that NO is involved in the thapsigargin-induced relaxation. Thapsigargin may deplete Ca2+ stores in the endothelial cells by inhibiting the CA2+-ATPase, a Ca2+ pump, which in turn triggers influx of extracellular Ca2+, leading to activation of constitutive NO synthase and resultant NO generation. The NO thus formed may activate soluble guanylate cyclase to produce cGMP in the vascular smooth muscle. 相似文献
7.
Yoshiki Takehara Hiroko Nakahara Shohei Okada Kiyonori Yamaoka Keisuke Hamazaki Akihiro Yamazato 《Free radical research》2013,47(4):287-294
Nitric oxide (NO) functions as an endothelium-derived relaxation factor and regulates vascular resistance. Recent studies in this laboratory (Arch. Biochem. Biophys. 323, 27–32, 1995) revealed that the lifetime of NO significantly increased at physiologically low levels of oxygen concentrations and, hence, this gaseous radical strongly inhibited mitochondrial electron transport for a fairly long duration at low oxygen concentrations. The present work describes the effect of oxygen concentration on NO-induced relaxation and guanylate cyclase (GC) activity of endothelium-denuded aorta of the rat. Both NO and 2,2′-hydroxynitrosohydrazono)bis-ethanamine (NOC18), an NO donor, induced the relaxa-tion of endothelium-denuded helical segments of rat aorta which were contracted by norepinephrine. NO-dependent relaxation of arterial specimens was enhanced by lowering oxygen concentration in the medium with concomitant increase in their cGMP levels. Anoxia induced the relaxation of the aorta by some NO-enhanceable and methylene blue-insensitive mechanism. These results suggested that local concentrations of oxygen might play important roles in the regulation of NO-dependent GC activity and vascular tonus of resistance arteries. 相似文献
8.
To investigate whether cyclic GMP (cGMP) would mediate, in an intracellular Ca2+ -dependent manner, coupling of auxin to stomatal opening, the stomatal opening responses to the auxin indolyl-3-butyric acid
(IBA) and to the cGMP membrane-permeable derivative 8-bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP) were compared in epidermal strips of Commelina communis. In this comparison were studied possible effects of intracellular Ca2+ modulators, GTP-binding protein (G-protein) modulators and selective inhibitors of enzymatic reactions which use or generate
cGMP. The stomatal response to IBA was almost similarly reversed by the Ca2+ buffer 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), the intracellular Ca2+-release inhibitors ruthenium red and procaine, the inactive cGMP analog Rp-8-bromoguanosine 3′,5′-cyclic monophosphorothioate (Rp-8-Br-cGMPS), the inhibitor of cGMP-producing guanylyl cyclase LY 83583, the G-protein inhibitor
mas17 and the G-protein antagonist pGlu-Gln-D-Trp-Phe-D-Trp-D-Trp-Met-NH2. Comparison with stomatal opening in response to 8-Br-cGMP, which was almost completely suppressed by either BAPTA, ruthenium
red, procaine or Rp-8-Br-cGMPS, strongly suggests that cGMP acts downstream of G-protein activation as a second messenger
for IBA signal transduction and that the cGMP pathway likely depends on cytosolic Ca2+signaling.
Received: 8 November 1997 / Accepted: 6 March 1998 相似文献
9.
Broughton BR Donald JA 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2005,175(3):157-166
This study examined the nitric oxide (NO) control of the vascular smooth muscle of the ventral abdominal vein and vena cava of the toad, Bufo marinus, by using anatomical and physiological approaches. Nicotinamide adenine di-nucleotide phosphate-diaphorase histochemistry and immunohistochemistry using endothelial nitric oxide synthase (NOS) and neural NOS antibodies produced no evidence for endothelial NOS in the veins, but, neural NOS-immunoreactive perivascular nerves were present. Acetylcholine (10–5 M) caused a vasodilation in both veins that was endothelium-independent, and which was blocked by the soluble guanylyl cyclase inhibitor, ODQ (10–5 M). The NOS inhibitors, L-NNA (10–4 M) and L-NAME (10–4 M), did not significantly reduce the vasodilatory effect of acetylcholine in the veins; this suggested that the vasodilation was not due to NO. However, in the presence of phenoxybenzamine (10–7–10–8 M), L-NNA significantly reduced the vasodilatory effect of acetylcholine in the veins. This unusual response is due to phenoxybenzamine partially inactivating the muscarinic receptor pool in the veins. In addition, the neural NOS inhibitor, vinyl-L-NIO (10–5 M), significantly reduced the acetylcholine-mediated vasodilation in the presence of phenoxybenzamine. The results show that in toad veins, nitrergic nerves rather than an endothelial NO system are involved in NO-mediated vasodilation. 相似文献
10.
M. A. Hossain W. Ye S. Munemasa Y. Nakamura I. C. Mori Y. Murata 《Plant biology (Stuttgart, Germany)》2014,16(6):1140-1144
Methyl jasmonate (MeJA) signalling shares several signal components with abscisic acid (ABA) signalling in guard cells. Cyclic adenosine 5′‐diphosphoribose (cADPR) and cyclic guanosine 3′,5′‐monophosphate (cGMP) are second messengers in ABA‐induced stomatal closure. In order to clarify involvement of cADPR and cGMP in MeJA‐induced stomatal closure in Arabidopsis thaliana (Col‐0), we investigated effects of an inhibitor of cADPR synthesis, nicotinamide (NA), and an inhibitor of cGMP synthesis, LY83583 (LY, 6‐anilino‐5,8‐quinolinedione), on MeJA‐induced stomatal closure. Treatment with NA and LY inhibited MeJA‐induced stomatal closure. NA inhibited MeJA‐induced reactive oxygen species (ROS) accumulation and nitric oxide (NO) production in guard cells. NA and LY suppressed transient elevations elicited by MeJA in cytosolic free Ca2+ concentration ([Ca2+]cyt) in guard cells. These results suggest that cADPR and cGMP positively function in [Ca2+]cyt elevation in MeJA‐induced stomatal closure, are signalling components shared with ABA‐induced stomatal closure in Arabidopsis, and that cADPR is required for MeJA‐induced ROS accumulation and NO production in Arabidopsis guard cells. 相似文献
11.
The present study was undertaken to assess the effects of sodium nitroprusside (SNP) and diethylamine NO(C2H5)2N[N(O)NO]−Na+ (DEA/NO), NO donors, on an acetylcholine (ACh)-induced Cl− current in identified Onchidium neurons using voltage-clamp and pressure ejection techniques. Bath-applied SNP (10 μM) and DEA/NO (5–10 μM) reduced the ACh-induced Cl− current in the neurons without affecting the resting membrane conductance and holding current. The suppressing effects of NO donors were concentration-dependent and completely reversible. Pretreatment with 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (1 μM), a specific inhibitor of NO-stimulated guanylate cyclase, and hemoglobin (50 μM), a nitric oxide scavenger, decreased the SNP-induced inhibition of the ACh-induced current. Intracellular injection of guanosine 3′,5′-cyclic monophosphate (cGMP) or bath-application of 3-isobutyl-1-methylxanthine (50 μM), a non-specific phosphodiesterase inhibitor, inhibited the ACh-induced current, mimicking the effect of NO donors. These results suggest that SNP and DEA/NO inhibit the ACh-induced Cl− current and that this effect is mediated by an increase in intracellular cGMP. © 1998 John Wiley & Sons, Inc. J Neurobiol 35: 388–394, 1998 相似文献
12.
Sakai T Michikawa H Furuyama S Sugiya H 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2002,132(4):801-809
Guanosine 3′,5′-monophosphate (cGMP) is an intracellular messenger in various kinds of cell. We investigated the regulation of cGMP production by nitric oxide (NO) in rabbit submandibular gland cells. Methacholine, a muscarinic cholinergic agonist, stimulated cGMP production in a dose- and time-dependent manner, but the α-agonist phenylephrine, substance P and the β-agonist isoproterenol failed to evoke cGMP production. In fura-2-loaded cells, methacholine induced an increase in intracellular Ca2+ ([Ca2+]i) in a concentration-dependent manner, which was similar to that for cGMP production. When the external Ca2+ was chelated with EGTA, methacholine failed to induce cGMP production. Ca2+ ionophore A23187 and thapsigargin, which induce the increase in [Ca2+]i without activation of Ca2+-mobilizing receptors, mimicked the effect of methacholine. cGMP production induced by methacholine, A23187 and thapsigargin was clearly inhibited by NG-nitro-
-arginine methylester (L-NAME), a specific inhibitor of nitric oxide synthase (NOS). S-Nitroso-N-acetyl-
-penicillamine (SNAP), a NO donor, induced cGMP formation. In the lysate of rabbit submandibular gland cells, Ca2+-regulated nitric oxide synthase activity was detected. These findings suggest that cGMP production induced by the activation of muscarinic cholinergic receptors is regulated by NO generation via the increase in [Ca2+]i. 相似文献
13.
Takeshi Minami Masayo Ichii Yoshiyuki Tohno Setsuko Tohno Masako Utsumi Masa-oki Yamada Yuko Okazaki 《Biological trace element research》1996,55(1-2):199-205
The purpose of this study was to determine the extent of aluminum (Al) accumulation in the human aorta and cerebral arteries.
The Al contents in the aortae and in the cerebral arteries from 23 human subjects was determined by inductively coupled plasma
atomic emission spectrophotometry (ICP-AES). The subjects' age range was 45–99-yr-old; 15 of the subjects were males and 8
were females. Al was detected in twelve aortae and in six cerebral arteries, when the entire specimen was analyzed. Two specimens
where Al was found in the cerebral arteries contained no Al in the aorta. No relationship to the subject's sex was found.
When related to age, two groups were established. Group L (45–75 yr old) and group H (>75 yr old), which exhibited aortal
Al concentrations of 33.3 and 72.7%, respectively. When the aortic wall was dissected into the tunica intima, media, and adventitia,
Al was found mainly in the tunica media. In the aorta, significant relationships were found between Al and phosphorus (P)
levels (r=0.801,p<0.01) and between Al and calcium (Ca) (r=0.661,p<0.05). We have concluded that Al accumulation is age-dependent and that it occurs both in the aorta and in the cerebral artery.
In the aorta, accumulation occurs mainly in the tunica media. Both P and Ca appear to enhance aortal Al accumulation. 相似文献
14.
Inhibition of nitric oxide synthase enhances contractile response of ventricular myocytes from streptozotocin-diabetic rats 总被引:1,自引:0,他引:1
The contractile hyporesponsiveness of the streptozotocin diabetic rat heart in vitro to β-adrenergic agonists is eliminated
when the heart is perfused with NG-nitro-l-arginine methyl ester (l-NAME), a non-selective inhibitor of nitric oxide synthase (NOS). The following study evaluated the hypothesis that an increased
production of NO/cGMP within the diabetic myocyte inhibits the β-adrenergic-stimulated increase in calcium current and contractile
response. Male Sprague-Dawley rats were given an intravenous injection of streptozotocin (60 mg/kg). After 8 weeks, L-type
calcium currents were recorded in ventricular myocytes using the whole cell voltage-clamp method. Shortening of isolated myocytes
was determined using a video edge detection system. cAMP and cGMP were measured using radioimmunoassay. Nitric oxide production
was determined using the Griess assay kit. Basal cGMP levels and nitric oxide production were elevated in diabetic myocytes.
Shortening of the diabetic myocytes in response to isoproterenol (1 μM) was markedly diminished. However, there was no detectable
difference in the isoproterenol-stimulated L-type calcium current or cAMP levels between control and diabetic myocytes. Acute
superfusion of the diabetic myocyte with l-NAME (1 mM) decreased basal cGMP and markedly enhanced the shortening response to isoproterenol but did not alter isoproterenol-stimulated
calcium current. These data suggest that increased production of NO/cGMP within the diabetic myocyte suppressed β-adrenergic
stimulated shortening of the myocyte. However, NO/cGMP apparently does not suppress shortening of the myocyte by inhibition
of the β-stimulated calcium current. 相似文献
15.
Jennings BL Bell JD Hyodo S Toop T Donald JA 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2007,177(5):557-567
This study investigated vasodilator mechanisms in the dorsal aorta of the elephant fish, Callorhinchus milii, using anatomical and physiological approaches. Nitric oxide synthase could only be located in the perivascular nerve fibres
and not the endothelium of the dorsal aorta, using NADPH histochemistry and immunohistochemistry. In vitro organ bath experiments
demonstrated that a NO/soluble guanylyl cyclase (GC) system appeared to be absent in the vascular smooth muscle, since the
NO donors SNP (10−4 mol l−1) and SIN-1 (10−5 mol l−1) were without effect. Nicotine (3 × 10−4 mol l−1) mediated a vasodilation that was not affected by ODQ (10−5 mol l−1), l-NNA (10−4 mol l−1), indomethacin (10−5 mol l−1), or removal of the endothelium. In contrast, the voltage-gated sodium channel inhibitor, tetrodotoxin (10−5 mol l−1), significantly decreased the dilation induced by nicotine, suggesting that it contained a neural component. Pre-incubation
of the dorsal aorta with the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP8–37 (10−6 mol l−1) also caused a significant decrease in the nicotine-induced dilation. We propose that nicotine is mediating a neurally-derived
vasodilation in the dorsal aorta that is independent of NO, prostaglandins and the endothelium, and partly mediated by CGRP. 相似文献
16.
Jian Wen Wang Li Ping Zheng Ben Zhang Ting Zou 《Applied microbiology and biotechnology》2009,85(2):285-292
This work examined the accumulation of artemisinin and related secondary metabolism pathways in hairy root cultures of Artemisia annua L. induced by a fungal-derived cerebroside (2S,2′R,3R,3′E,4E,8E)-1-O-β-d-glucopyranosyl-2-N-(2′-hydroxy-3′-octadecenoyl)-3-hydroxy-9-methyl-4,8-sphingadienine. The presence of the cerebroside induced nitric oxide
(NO) burst and artemisinin biosynthesis in the hairy roots. The endogenous NO generation was examined to be involved in the
cerebroside-induced biosynthesis of artemisinin by using NO inhibitors, N
ω-nitro-l-arginine methyl ester and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. The gene expression and activity
of 3-hydroxy-3-methylglutaryl CoA reductase and 1-deoxy-d-xylulose 5-phosphate synthase were stimulated by the cerebroside, but more strongly by the potentiation of NO. While the
mevalonate pathway inhibitor, mevinolin, only partially inhibited the induced artemisinin accumulation, the plastidic 2-C-methyl-d-erythritol 4-phosphate pathway inhibitor, fosmidomycin, nearly arrested artemisinin accumulation induced by cerebroside and
the combination elicitation with an NO donor, sodium nitroprusside (SNP). With the potentiation by SNP at 10 μM, the cerebroside
elicitor stimulated artemisinin production in 20-day-old hairy root cultures up to 22.4 mg/l, a 2.3-fold increase over the
control. These results suggest that cerebroside plays as a novel elicitor and the involvement of NO in the signaling pathway
of the elicitor activity for artemisinin biosynthesis. 相似文献
17.
Brief limb ischemia was reported to protect neurons against injury induced by subsequent cerebral ischemia-reperfusion, and
this phenomenon is known as limb ischemic preconditioning (LIP). To explore the role of nitric oxide (NO) in neuroprotection
of LIP in rats, we observed changes in the content of nitric oxide (NO) and activity of NO synthase (NOS) in the serum and
CA1 hippocampus of rats after transient limb ischemic preconditioning (LIP), and the influence of NG-nitro-l-arginine methylester (l-NAME), a NOS inhibitor, on the neuroprotection of LIP against cerebral ischemia-reperfusion injury. Results showed that NO
content and NOS activity in serum increased significantly after LIP compared with the sham group. The increase showed a double
peak pattern, in which the first one appeared at time 0 (immediate time point) and the second one appeared at 48 h after the
LIP (P < 0.01). The NO content and NOS activity in the CA1 hippocampus in LIP group showed similar change pattern with the changes
in the serum, except for the first peak of up-regulation of NO content and NOS activity appeared at 6 h after LIP. Pretreatment
with l-NAME before LIP blocked the neuroprotection of LIP against subsequent cerebral ischemic insult. The blocking effect of l-NAME was abolished with pretreatment of l-Arg. These findings indicated that NO may be associated with the tolerance of pyramidal cells in the CA1 hippocampus to ischemia
induced by LIP in rats. 相似文献
18.
Hilgier W Wegrzynowicz M Maczewski M Beresewicz A Oja SS Saransaari P Albrecht J 《Neurochemical research》2008,33(2):267-272
Ammonia neurotoxicity is associated with overactivation of N-methyl-d-aspartate (NMDA) receptors leading to enhanced nitric oxide and cyclic GMP synthesis and to accumulation of reactive oxygen
and nitrogen species. Ammonia is detoxified in the brain via synthesis of glutamine, which if accumulated in excess contributes
to astrocytic swelling, mitochondrial dysfunction and cerebral edema. This study was aimed at testing the hypothesis that
the activity of the NMDA/NO/cGMP pathway is controlled by the ammonia-induced production of Gln in the brain. Ammonium chloride
(final concentration 5 mM), infused for 40 min to the rat striatum via a microdialysis probe, caused a significant increase
in Gln (by 40%), NO oxidation products (nitrite+nitrate = NOx) (by 35%) and cGMP (by 50%) concentration in the microdialysate. A Gln synthetase inhibitor, methionine sulfoximine (MSO,
5 mM), added directly to the microdialysate, completely prevented ammonia-mediated production of Gln, and paradoxically, it
increased ammonia-mediated production of NOx and cGMP by 230% and 250%, respectively. Of note, MSO given alone significantly reduced basal Gln concentration in the rat
striatum, had no effect on the basal NOx concentration, and attenuated basal concentration of cGMP in the microdialysate by 50%. The results of the present study
suggest that Gln, at physiological concentrations, may ameliorate excessive activation of the NO–cGMP pathway by neurotoxic
concentrations of ammonia. However, in view of potential direct interference of MSO with the pathway, exogenously added Gln
and less toxic modulators of Gln content and/or transport will have to be employed in further studies on the underlying mechanisms.
Special issue article in honor of Dr. Frode Fonnum.
Wojciech Hilgier and Michal Węgrzynowicz contributed equally to this work. 相似文献
19.
Curto-Reyes V Juárez L García-Pérez E Fresno MF Hidalgo A Menéndez L Baamonde A 《Cellular and molecular neurobiology》2008,28(7):981-990
The stimulation of peripheral opioid receptors counteracts thermal hyperalgesia produced by the intratibial inoculation of
NCTC 2472 cells in mice, through the activation of the nitric oxide/cGMP/ATP-sensitive K+-channels (NO/cGMP/K+
ATP) cascade (Menéndez et al. 2007, Neuropharmacology 53:71–80). We aimed to elucidate whether this peripheral opioid antihyperalgesic effect is exclusive to
this model or might also occur in other types of bone neoplastic processes. In C57BL/6 mice intratibially inoculated with
B16-F10 melanoma cells, the progressive tumoral damage was accompanied by the establishment of thermal hyperalgesia (unilateral
hot plate test) and mechanical allodynia (von Frey test). Intraplantar administration of loperamide (15 μg, 30 min before)
inhibited thermal hyperalgesia, but did not modify the intense mechanical allodynia. The fact that the coadministration of
naloxone-methiodide (5 μg) completely suppressed the thermal antihyperalgesic effect induced by loperamide indicates its production
through the stimulation of peripheral opioid receptors. Furthermore, its prevention by the coadministration of the non-selective
inhibitor of the NO synthase, NG-monomethyl-L-arginine (L-NMMA, 10 μg), the selective inhibitor of neural NOS, N-ω-propyl-L-arginine (1–10 μg), or the K+
ATP channel blocker, glibenclamide (10 μg) demonstrated the involvement of the NO/cGMP/K+
ATP pathway in the antihyperalgesic effect induced by loperamide. Overall, the present results show that the intratibial inoculation
of B16-F10 cells to C57BL/6 mice evokes thermal hyperalgesia and mechanical allodynia and that, as occurred in the osteosarcoma
model, the stimulation of peripheral opioid receptors is not effective in modifying neoplastic allodynia but completely inhibits
thermal hyperalgesia through the activation of the NO/cGMP/K+
ATP cascade. 相似文献
20.
Theresa Siegl Joachim Schachtner Gay R. Holstein Uwe Homberg 《Cell and tissue research》2009,337(2):327-340
Nitric oxide (NO) is a gaseous messenger molecule formed during conversion of L-arginine into L-citrulline by the enzyme NO synthase (NOS), which belongs to a group of NADPH diaphorases. Because of its gaseous diffusion
properties, NO differs from classical neurotransmitters in that it is not restricted to synaptic terminals. In target cells,
NO activates soluble guanylyl cyclase leading to an increase in cGMP levels. In insects, this NO/cGMP-signalling pathway is
involved in development, memory formation and processing of visual, olfactory and mechanosensory information. We have analysed
the distribution of putative NO donor and target cells in the central complex, a brain area involved in sky-compass orientation,
of the locust Schistocerca gregaria by immunostaining for L-citrulline and cGMP. Six types of citrulline-immunostained neurons have been identified including a bilateral pair of hitherto
undescribed neurons that connect the lateral accessory lobes with areas anterior to the medial lobes of the mushroom bodies.
Three-dimensional reconstructions have revealed the connectivity pattern of a set of 18 immunostained pontine neurons of the
central body. All these neurons appear to be a subset of previously mapped NADPH-diaphorase-positive neurons of the central
complex. At least three types of central-complex neurons show cGMP immunostaining including a system of novel columnar neurons
connecting the upper division of the central body and the lateral triangle of the lateral accessory lobe. Our results provide
the morphological basis for further studies of the function of the labelled neurons and new insights into NO/cGMP signalling.
This work was supported by DFG grant HO 950/16-2. 相似文献