Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies suggested that the L-arginine/nitric oxide (NO)/cyclic GMP pathway is involved in the modulation of pain perception. The present experiments were undertaken to find out the role of this pathway in the antinociception induced by oxotremorine administration. Male mice of the CD-1 strain were injected with different doses of the muscarinic agonist oxotremorine (0.005, 0.01, 0.02, 0.03 mg/kg i.p.) 5 min after the administration of saline solution or the inhibitors of NO synthase NG-nitro-L-arginine methyl ester (L-NAME: 10 and 20 mg/kg, i.p.) or NG-nitro-L-arginine (N-ARG: 10 and 20 mg/kg i.p.). Oxotremorine induced a dose- and time-dependent analgesic effect in mice, which was significantly increased by L-NAME and N-ARG administration. Either doses of the NO inhibitors given alone had no effect on the nociceptive threshold. The present results show a role of NO in the antinociception mediated by the muscarinic receptor stimulation and suggest that it exerts an inhibitory action on cholinergic analgesia.
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PMID:Nitric oxide synthase inhibitors enhance the antinociceptive effects of oxotremorine in mice. 943 49

The aim of this study was to evaluate whether acetylcholine induces NO release. We determined the responses on the cholinergic component of the response to electrical field stimulation (EFS) the effects of L-nitro-arginine-methyl-ester (L-NAME; 1 mM), an inhibitor of NO synthase, of L-Arginine (L-ARG; 1 mM), a precursor of NO synthesis, and methoctramine (0.01-0.1-1 microM), an antagonist of M2 receptors, alone or associated with L-NAME. The experiments were performed on guinea pig isolated intact- or denuded-epithelium tracheal rings contracted in a frequency-dependent manner to EFS. At the maximum frequency tested (30 Hz), the contractile response elicited was 60.36 +/- 0.61% of acetylcholine (100 microM) contraction, while the maximal relaxant effect induced by EFS was -28.40 +/- 0.61% in epithelium intact preparations. A pretreatment with L-NAME significantly (P<0.05) increased the contraction (76.08 +/- 1.39%) and reduced the relaxation elicited by EFS. L-NAME effect on both EFS induced responses were statistically (P<0.05) reversed by the association L-NAME + L-ARG. Methoctramine (1 microM) enhanced contractile (P<0.05) (79.20 +/- 2.21%), as well as relaxant responses (-38.73 +/- 0.99%) elicited by EFS in guinea pig epithelium-intact tracheal rings; in a separate series of experiments, performed on guinea pig epithelium-intact rings, L-NAME increased the contractile responses to methoctramine (82.6 +/- 2.31), but reduced the relaxant ones (26.38 +/- 1.29). In contrast, at the maximum frequency tested, it increased only the contractile response, but not modify the relaxant one, in epithelium denuded rings. In conclusion, the present data showed that the release of acetylcholine from postganglionic cholinergic nerves plays an important role on NO formation and this effect may be modulate by epithelium.
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PMID:Possible functional modulation by acetylcholine of nitric oxide on guinea pig isolated trachea. 946 68

The effect of L-arginine (L-ARG), a nitric oxide donor, or Nomega-nitro-L-arginine (L-NAME), a nitric oxide synthase inhibitor, on the regulation of kainic acid (KA)-induced proenkephalin (proENK) and prodynorphin (proDYN) mRNA expressions in rat hippocampus was studied. The proENK and proDYN mRNA levels were markedly increased 6 h after KA (10 mg/kg, i.p.) administration. The elevations of both proENK and proDYN mRNA levels induced by KA was effectively inhibited by pre-administration of L-ARG (400 mg/kg, i.p.), but was not affected by pre-treatment with L-NAME (200 mg/kg, i.p.). The blockade of KA-induced proENK and proDYN mRNA levels by the pre-treatment with L-ARG was well correlated with proto-oncoprotein levels, such as c-Fos, Fra-2, FosB, JunD, JunB, and c-Jun, as well as AP-1 and ENKCRE-2 DNA binding activities. The pre-administration with L-NAME further increased KA-induced c-jun and c-fos mRNA levels in addition to their protein product levels, although the pre-treatment with L-NAME did not affect KA-induced FosB, Fra-2, JunB, and JunD protein levels at 6 h after treatment. In addition, the pre-administration with L-NAME further increased the KA-induced AP-1 and ENKCRE-2 DNA binding activities. Our results suggest that L-ARG plays an important role in inhibiting KA-induced proENK or proDYN mRNA expression, and its inhibitory action may be mediated through reducing the proto-oncoprotein levels, such as c-Fos, Fra-2, FosB, c-Jun, JunD, and JunB. In addition, L-NAME potentiated the c-Fos or c-Jun gene expression, as well as AP-1 or ENKCRE-2 DNA binding activity. However, these increases did not show the potentiative effect on KA-induced increases of proENK and proDYN mRNA level.
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PMID:The modulatory role of nitric oxide in the regulation of proenkephalin and prodynorphin gene expressions induced by kainic acid in rat hippocampus. 960 69

A microinjection of endothelin-1 (ET-1; 10 pmol) into the superior colliculus (SC) of anaesthetised rats caused a decrease in blood pressure. Microinjection into the same nucleus of Nomega-nitro-L-arginine methyl ester (L-NAME; 0.1, 0.5, 1 micromol), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) synthase, increased the basal mean arterial blood pressure. Treatment of SC with L-NAME (1 micromol) did not affect the depressor response induced by injection of ET-1 (10 pmol), into the SC, at the peak of the pressor response to L-NAME. In addition, L-arginine L-ARG) (1 micromol), the substrate for NO synthase, microinjected into the superior colliculus prior to ET-1 did not significantly increase the depressor response to ET-1. These findings, therefore, suggest that within the SC the nitric oxide synthesis does not affect depressor responses induced by ET-1.(c) 1998 The Italian Pharmacological Society
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PMID:Nitric oxide synthesis does not affect depressor responses induced by endothelin-1 into the superior colliculus of rats. 980 15

We examined potential mechanisms by which angiotensin subtype-2 (AT2) receptor stimulation induces net fluid absorption and serosal guanosine cyclic 3',5'-monophosphate (cGMP) formation in the rat jejunum. L-arginine (L-ARG) given intravenously or interstitially enhanced net fluid absorption and cGMP formation, which were completely blocked by the nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine methylester (L-NAME), but not by the specific AT2 receptor antagonist, PD-123319 (PD). Dietary sodium restriction also increased jejunal interstitial fluid cGMP and fluid absorption. Both could be blocked by PD or L-NAME, suggesting that the effects of sodium restriction occur via ANG II at the AT2 receptor. L-ARG-stimulated fluid absorption was blocked by the soluble guanylyl cyclase inhibitor 1-H-[1,2,4]oxadiazolo[4, 2-alpha]quinoxalin-1-one (ODQ). Cyclic GMP-specific phosphodiesterase in the interstitial space decreased extracellular cGMP content and prevented the absorptive effects of L-ARG. Angiotensin II (ANG II) caused an increase in net Na+ and Cl- ion absorption and 22Na+ unidirectional efflux (absorption) from the jejunal loop. In contrast, intraluminal heat-stable enterotoxin of Escherichia coli (STa) increased loop cGMP and fluid secretion that were not blocked by either L-NAME or ODQ. These findings suggest that ANG II acts at the serosal side via AT2 receptors to stimulate cGMP production via soluble guanylyl cyclase activation and absorption through the generation of NO, but that mucosal STa activation of particulate guanylyl cyclase causes secretion independently of NO, thus demonstrating the opposite effects of cGMP in the mucosal and serosal compartments of the jejunum.
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PMID:Compartmentalization of extracellular cGMP determines absorptive or secretory responses in the rat jejunum. 991 28

Mechanisms responsible for the pulsatile release of gonadotrophin secretion in prepubertal heifers are not fully known. We have shown that an excitatory amino acid agonist, N-Methyl-D,L-aspartic acid (NMA), induces an immediate release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) in prepubertal heifers. Nitric oxide (NO) has also emerged as an important regulator of LH release in rats. This study was designed to test the role of NO in the regulation of gonadotrophin release as well as the possible mediation by NO of the effects of NMA and gonadotrophin releasing hormone (GnRH) on gonadotrophin secretion in heifer calves. In experiment 1, four groups of five prepubertal heifers (33 weeks old) received one of the following treatments: (1); N-G-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor, 35 mg/kg, i.v., once); (2) NMA (4.7 mg/kg, i.v., once); (3) L-NAME+NMA (as above); and (4) Vehicle (saline, i.v.). All heifers in all groups were also challenged with a bolus injection of GnRH (10 ng/kg, i.v., once). Blood samples were collected every 15 min for 10 h. L-NAME was injected after the first blood sample, NMA after 2 h and GnRH after 6 h of blood sampling. Administration of L-NAME alone, suppressed the spontaneous pulses of LH (P<0.04). Heifers in the NMA group responded with a significantly greater LH release than did the heifers in the L-NAME+NMA group (P<0.05). Following the GnRH challenge, heifer calves treated with L-NAME or NMA had higher LH pulse responses than the controls (P<0.05). In a second experiment, four groups of five heifer calves (34 weeks old) were given one of the following treatments: (1) L-NAME (as above); (2) L-arginine, a NO precursor (ARG, 100 mg/kg/h, i.v. drip infused for 6 h starting 2 h after first blood sample was taken); (3) L-NAME+ARG (as above); and (4) Vehicle (saline i.v. bolus and drip for 6 h). Blood samples were taken every 10 min for 8 h. Administration of L-NAME suppressed the pulsatile release of LH and FSH (P<0.05). Compared to the control group, infusion of ARG by itself did not change the pattern of LH secretion (P>0.05); however, in heifers given L-NAME, ARG restored a normal pattern of LH pulses, similar to the control values (P>0.05). It was therefore concluded that NO is involved in the regulation of LH, and possibly FSH, secretion and that NO may mediate, at least in part, the stimulatory effects of NMA on LH, and to some extent FSH, release. The responses to GnRH led us to suggest that NO may have inhibitory effects on the pituitary and NMA may have increased pituitary sensitivity to GnRH.
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PMID:Nitric oxide regulation of gonadotrophin secretion in prepubertal heifers1. 1044 5

The effects of bath application of the nitric oxide (NO) precursor L-arginine (L-ARG) on the resting activity (RA) of afferent crista fibers were studied in isolated statocysts of the cuttlefish Sepia officinalis under various experimental conditions. L-ARG (threshold 10(-7) M) had three different effects: inhibition, excitation, and excitation followed by an inhibition; only the inhibitory effect of L-ARG was dose-dependent. D-Arginine (D-ARG) had no effect. When the preparation was pre-treated with NO synthase inhibitors (N(G)-Nitric-L-arginine methyl ester HCl (L-NAME), N(G)-Nitro-L-arginine (L-NOARG)), both the inhibitory and the excitatory effects of L-ARG significantly decreased at higher concentrations (10(-5 to -4) M), or were completely blocked at lower concentrations (10(-7 to -6) M), of L-ARG. When the preparation was pre-treated with guanylate cyclase inhibitors (1H-[1,2, 4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), methylene blue (M-BLU), cystamine (CYS)), L-ARG had only excitatory effects, whereas its effects were only inhibitory when the preparation was pre-treated with adenylate cyclase inhibitors 2',3'-dideoxyadenosine (DDA), MDL-12330A (MDL), nicotinic acid (NIC-A)). L-ARG had no effects when the pre-treatment was with a guanylate cyclase inhibitor and an adenylate cyclase inhibitor combined; in that situation, the RA of the afferent fibers remained. These data indicate that in cephalopod statocysts, a cGMP and a cAMP signal transduction pathway (presumably via the generation of NO) are responsible for the effects of L-ARG on the RA of crista afferent fibers. They also indicate that the L-ARG-cGMP pathway is the dominant pathway and is inhibitory, and that both pathways have only modulatory effects on, but are not essential for, the generation of the RA.
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PMID:Effects of L-arginine on the afferent resting activity in the cephalopod statocyst. 1052 42

In the present study, nonadrenergic, noncholinergic (NANC) responses of rabbit detrusor smooth muscle and the possible involvement of the L-arginine/nitric oxide (L-ARG/NO) pathway was investigated. In the presence of atropine (10(-6) M) and guanethidine (10(-5) M), frequency-response curves were obtained by stimulating tissue with 10-sec trains at increasing frequencies (1-10 Hz) with 3-min intervals between stimulations. Electrical field stimulation (EFS) evoked a biphasic response in rabbit detrusor smooth muscle, consisting of an initial contraction followed by relaxation. ATP desensitization significantly inhibited contractions. L-NAME (10(-5) M) increased the contractions by a maximum of 33 +/- 5% at 1 Hz, 37 +/- 5% at 2 Hz, 18 +/- 4% at 4 Hz, 20 +/- 3% at 8 Hz and 15 +/- 4% at 10 Hz. In detrusor preparations, exposure to L-NAME (NG-nitro-L-arginine methyl ester, 10(-5) M) significantly reduced the maximal relaxation to electrical stimulation to 7 +/- 3% of the control. In the presence of L-ARG (10(-4) M), contractions induced by electrical field stimulation (EFS) at 1, 2, 4, 8 and 10 Hz were reduced by 20 +/- 4, 24 +/- 3, 25 +/- 3, 20 +/- 3 and 30 +/- 5%, respectively. Exposure to L-ARG (10(-4) M) significantly increased the maximal relaxation to electrical stimulation to 52 +/- 5% of the control. Exogenously applied ATP (10(-5)-10(-2) M) to rabbit detrusor muscle resulted in contractions while sodium nitroprusside (10(-7)-10(-3) M) caused concentration-dependent relaxation. These results suggest that nitric oxide (NO) acts as an inhibitory NANC neurotransmitter in the rabbit detrusor smooth muscle. Additionally, NANC contractions mediated by ATP released from NANC nerves, may be masked by the L-ARG/NO pathway in this tissue.
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PMID:Nonadrenergic, noncholinergic responses of the rabbit detrusor smooth muscle and the role of L-arginine/nitric oxide pathway in these responses. 1079 Dec 92

The aim of the present study was to investigate the possible role of nitric oxide (NO) as a nonadrenergic, noncholinergic (NANC) mediator in human colon smooth muscle in vitro and to examine its possible interactions with K+ channels. In the presence of atropine (10(-6) M) and guanethidine (10(-5) M), electrical field stimulation (EFS, 1-10 Hz, 0.3 msec, 50 V) for 10 sec induced relaxations which were inhibited by tetrodotoxin (10(-6) M). In the presence of NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), relaxations induced by EFS at 1, 2, 4, 8 and 10 Hz were reduced by 38.7 +/- 4.3, 31.5 +/- 3.8, 54.3 +/- 5.4, 59.8 +/- 4.5 and 68.6 +/- 5.3%, respectively. The relaxations inhibited by L-NAME were restored by the preincubation of L-arginine (L-ARG, 10(-3) M) at all frequencies tested. D-Arginine (D-ARG, 10(-3) M) had no effect. Tetraethylammonium (TEA, 10(-4) M) or glibenclamide (10(-6) M) significantly decreased the relaxations induced by EFS. Exogenously applied sodium nitroprusside caused concentration-dependent relaxation with maximum relaxation observed with 10(-3) M. TEA (10(-4) M) and glibenclamide (10(-6) M) significantly depressed the maximum response to sodium nitroprusside. In conclusion, our data indicate that NO is involved in NANC nerve-mediated relaxation in the human colon smooth muscle and the relaxant responses to endogenously released or exogenously applied NO are mediated, in part, by activation of calcium-dependent and ATP-sensitive K+ channels.
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PMID:Nonadrenergic, noncholinergic responses of the human colon smooth muscle and the role of K+ channels in these responses. 1141 58

The physiological role of nitric oxide in the control of striatal dopamine release has not been fully established, therefore, the effect of neuronally produced nitric oxide (NO) on striatal dopamine (DA) efflux were investigated using in vivo microdialysis in anaesthetised and conscious rats. In the anaesthetised rat, the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methylester (L-NAME) and 7-nitroindazole monosodium salt (7-NINA) produced concentration-dependent increases in DA efflux. The L-NAME (1 mM)- and 7-NINA (1 mM)-induced increase was reduced by co-administration with the NO precursor, L-arginine (L-ARG; 1 mM) by 37% and 54% respectively, and was prevented by tetrodotoxin (TTX, 1 microM). Similarly, in conscious rats, L-NAME (1 mM) and 7-NINA (1 mM) increased DA efflux to 161% and 166% of basal efflux respectively. These data suggest that neuronally produced NO inhibits striatal DA efflux through an indirect mechanism.
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PMID:Inhibition of neuronal nitric oxide synthase increases dopamine efflux from rat striatum. 1265 63


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