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)

1. The mechanisms involved in the antinociceptive action of L-NG-nitro arginine methyl ester (L-NAME) were investigated in mice. 2. Intraperitoneal administration of L-NAME produced a dose-dependent antinociception in the tail-flick, hot-plate and phenyl-p-quinone-induced writhing tests. 3. Pretreatment with the catecholamine depletors 6-hydroxydopamine (5 micrograms i.c.v.) or reserpine (5 mg/kg i.p.) or the serotonin synthesis inhibitor, p-chlorophenylalanine methyl ester (200 mg/kg i.p. on 2 consecutive days) resulted in a significant decrease in the antinociceptive effect of L-NAME. 4. Similarly, pretreatment with the selective alpha 1-adrenoceptor antagonist prazonin (2.5 mg/kg, i.p.), or the non-selective alpha-adrenoceptor blocker, phentolamine (5 mg/kg, i.p.) antagonized the antinociceptive effect of L-NAME. 5. However, the administration of the selective alpha 2-adrenoceptor antagonist, idazoxan (2.5 mg/kg i.p.) was without effect. 6. Likewise, pretreatment with the serotonin 5-HT2 receptor blocker, ketanserin (1 mg/kg, i.p.), the D2 dopamine receptor antagonist (+/-) sulpiride (30 mg/kg, i.p.) or the opioid antagonist naloxone (5 mg/kg, i.p.) did not inhibit the antinociceptive effect of L-NAME. 7. These results suggest that L-NAME produces antinociception in the mouse probably by an action on adrenergic and serotonergic synapses.
Gen Pharmacol 1992 Nov
PMID:Mechanisms of L-NG-nitro arginine methyl ester-induced antinociception in mice: a role for serotonergic and adrenergic neurons. 136 51

CAR and C1, two carrot (Daucus carota L.) suspension cultures of different genotypes, were subjected to stepwise selection for tolerance to the herbicide glyphosate [(N-phosphonomethyl)glycine]. The specific activity of the target enzyme, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), as well as the mRNA level and copy number of the structural gene increased with each glyphosate selection step. Therefore, the tolerance to glyphosate is due to stepwise amplification of the EPSPS genes. During the amplification process, DNA rearrangement did not occur within the EPSPS gene of the CAR cell line but did occur during the selection step from 28 to 35 mM glyphosate for the C1 cell line, as determined by Southern hybridization of selected cell DNA following EcoRI restriction endonuclease digestion. Two cell lines derived from a previously selected glyphosate-tolerant cell line (PR), which also had undergone EPSPS gene amplification but have been maintained in glyphosate-free medium for 2 and 5 years, have lost 36 and 100% of the increased EPSPS activity, respectively. Southern blot analysis of these lines confirms that the amplified DNA is relatively stable in the absence of selection. These studies demonstrate that stepwise selection for glyphosate resistance reproducibly produces stepwise amplification of the EPSPS genes. The relative stability of this amplification indicates that the amplified genes are not extrachromosomal.
Mol Gen Genet 1992 Apr
PMID:Glyphosate selected amplification of the 5-enolpyruvylshikimate-3-phosphate synthase gene in cultured carrot cells. 137 13

The biochemical signaling pathways involved in nitric oxide (NO)-mediated cholinergic inhibition of L-type Ca2+ current (ICa[L]) were investigated in isolated primary pacemaker cells from the rabbit sinoatrial node (SAN) using the nystatin-perforated whole-cell voltage clamp technique. Carbamylcholine (CCh; 1 microM), a stable analogue of acetylcholine, significantly inhibited ICa(L) after it had been augmented by isoproterenol (ISO; 1 microM). CCh also activated an outward K+ current, IK(ACh). Both of these effects of CCh were blocked completely by atropine. Preincubation of the SAN cells with L-nitro-arginine methyl ester (L-NAME; 0.2-1 mM), which inhibits NO synthase (NOS), abolished the CCh-induced attenuation of ICa(L) but had no effect on IK(ACh). Coincubation of cells with both L-NAME and the endogenous substrate of NOS, L-arginine (1 nM), restored the CCh-induced attenuation of ICa(L), indicating that L-NAME did not directly interfere with the muscarinic action of CCh on ICa(L). In the presence of ISO the CCh-induced inhibition of ICa(L) could be mimicked by the NO donor 3-morpholino-sydnonimine (SIN-1; 0.1 mM). SIN-1 had no effect on its own or after a maximal effect of CCh had developed, indicating that it does not inhibit ICa(L) directly. SIN-1 failed to activate IK(ACh), demonstrating that it did not activate muscarinic receptors. Both CCh and NO are known to activate guanylyl cyclase and elevate intracellular cGMP. External application of methylene blue (10 microM), which interferes with the ability of NO to activate guanylyl cyclase, blocked the CCh-induced attenuation of ICa(L). However, it also blocked the activation of IK(ACh), suggesting an additional effect on muscarinic receptors or G proteins. To address this, a separate series of experiments was performed using conventional whole-cell recordings with methylene blue in the pipette. Under these conditions, the CCh-induced attenuation of ICa(L) was blocked, but the activation of IK(ACh) was still observed. Methylene blue also blocked the SIN-1-induced decrease in ICa(L). 6-anilino-5,8-quinolinedione (LY83583; 30 microM), an agent known to decrease both basal and CCh-stimulated cGMP levels, prevented the inhibitory effects of both CCh and SIN-1 on ICa(L), but had no effect on the activation of IK(ACh) by CCh. In combination, these results show that CCh- and NO-induced inhibition of ICa(L) is mediated by cGMP.(ABSTRACT TRUNCATED AT 400 WORDS)
J Gen Physiol 1995 Jul
PMID:A cellular mechanism for nitric oxide-mediated cholinergic control of mammalian heart rate. 749 38

1. This study directly compares the response of cavernosal tissue obtained from sexually mature rabbits with the response of human corpus cavernosal tissue obtained during implant surgery for psychogenic impotence (five individual samples) to field stimulation and specific autonomic agonists. 2. At 2 g basal tension, field stimulation of the rabbit corpus cavernosal tissue produced a frequency dependent biphasic response consisting of an initial relaxation followed by contraction. Low frequency stimulation induced primarily relaxations whereas high frequency stimulation induced primarily contractions. FS of human corpus cavernosal tissue induced a frequency dependent contraction. 3. In general, the rabbit corpus cavernosal strips showed a significantly greater degree of spontaneous activity than the strips of human cavernosal tissue. 4. Phenylephrine stimulated a rapid and sustained increase in basal tension in both tissues. Although the isolated strips weighed the same, the magnitude of the response of the rabbit tissue was significantly greater than the response of the human tissue. 5. For both tissues, FS relaxations were completely inhibited by L-NAME showing that the relaxations were mediated by nitric oxide. Similarly, for both tissues, nitroprusside, ATP, and bethanechol induced similar dose-response relaxations of pre-stimulated tissue. 6. In conclusion, the major difference between the response of human and rabbit tissue to various forms of stimulation was that isolated strips of human corporal tissue responded to FS with contractions at all frequencies whereas the rabbit tissue responded to the relaxations at low frequencies of stimulation; a clear bi-phasic response at intermediate frequencies; and contraction at high frequencies.
Gen Pharmacol 1995 Sep
PMID:Comparison of the pharmacological response of human corpus cavernosal tissue with the response of rabbit cavernosal tissue. 755 58

1. The aim of the present study was to evaluate the role of NO in the cardiovascular effects of adenosine in conscious rats. 2. Cardiac index was determinated by thermodilution. In a group of rats, three doses of adenosine were infused (i.v.) at a rate of 150, 300 and 450 micrograms/kg/min in the absence and in the presence of L-NAME (10 mg/kg). In a second group of rats, the experimental protocol was the same as that of the first group, except an infusion of methoxamine (50 micrograms/kg/min) was given during the second adenosine administration, instead of L-NAME. 3. In the absence of L-NAME or methoxamine, adenosine induced a dose-dependent decrease in mean arterial pressure and an increase in vascular conductance although adenosine did not affect cardiac index. 4. L-NAME administration attenuated the decreasing effect on the mean arterial pressure in response to the two lower doses of adenosine. In the presence of L-NAME, adenosine induced a significant increase in cardiac index from 18.7 +/- 1.5 to 29.1 +/- 1.9 and 26.2 +/- 1.4 ml/min/100 g. Administration of L-NAME significantly attenuated the adenosine-induced increase in vascular conductance. 5. Methoxamine infusion induced an enhanced response to adenosine infusion. In the presence of methoxamine, adenosine induced a significant greater decrease in mean arterial pressure, and increase in cardiac index and vascular conductance. 6. These results indicate that part of the cardiovascular effects of adenosine can be mediated by NO, since L-NAME administration partially blocked the adenosine-induced vasodilatation.
Gen Pharmacol 1995 Jan
PMID:Effect of N omega-nitro-L-arginine methyl ester on cardiac haemodynamic responses to adenosine infusion in conscious rats. 771 54

1. We examined the contribution of endothelium-derived hyperpolarizing factor (EDHF) to the impairment of endothelium-dependent relaxation caused by acetylcholine (ACh) in the aorta of streptozotocin-induced diabetic rats, by using N omega-L-nitro-arginine methylester (L-NAME) and tetraethylammonium chloride (TEA) to inhibit nitric oxide (NO) and EDHF, respectively. 2. ACh-induced relaxation of the aorta decreased in diabetic rats. In contrast, sodium nitroprusside-induced relaxation was the same in diabetic rats and control rats. 3. Treatment with 5 x 10(-7) M L-NAME resulted in a right shift of the dose-response curves of ACh-induced relaxation in the aorta. The shift was greater in the control aorta. 4. Treatment with 5 x 10(-4) M TEA resulted in a similar right shift in both the control and diabetic aorta. 5. Therefore, while endothelium-derived NO appears to contribute to the impairment of ACh-induced endothelium-dependent relaxation in the aorta of diabetic rats, EDHF does not.
Gen Pharmacol 1995 Jan
PMID:Endothelium-derived hyperpolarizing factor does not contribute to the decrease in endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic rats. 771 55

1. AI and AII induced contractions in cat femoral arteries, which were inhibited by saralasin. 2. The response to AI was reduced by captopril and endothelium removal and by chymostatin in endothelium-denuded segments. 3. AII contractions were increased by indomethacin, L-NAME and endothelium removal. 4. AII and AI facilitated the adrenergic neurotransmission. This facilitation was inhibited by saralasin and/or captopril. 5. These data suggest: (1) AI is converted into AII in the endothelial and adventitial layer; (2) the contractions caused by AI and AII are mediated by AII receptors and are modulated by endothelial release of NO and PGI2; and (3) the existence of presynaptic AII receptors mediating the facilitation of neurotransmission caused by AI and AII.
Gen Pharmacol 1994 Dec
PMID:Angiotensin modulation of vascular tone and adrenergic neurotransmission in cat femoral arteries. 772 Oct 47

1. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO biosynthesis, which blocks basal NO production, caused a similar increase of mean arterial pressure (MAP) in control hyper- and hypothyroid rats at the lowest dose, however, smaller pressor effects were observed with increasing doses in hyper- and hypothyroid rats. An additional dose of L-NAME (30 mg/kg), which produced no further increase in pressure, killed 90% of the hyperthyroid rats, whereas hypothyroid and control rats survived this additional dose. 2. The systemic responses to acetylcholine (ACh), an endothelium-dependent vasodilator that stimulates NO production/release, were significantly increased in hypothyroid rats, while hyperthyroid rats showed no significant differences when compared with controls. However, 10(-8) M ACh killed hyperthyroid rats, whereas control and hypothyroid rats survived this dose. 3. The maximal hypotensive response to sodium nitroprusside (SNP), an agonist that generates NO, was similar in intact controls, hyper- and hypothyroid rats. 4. These data indicate that hyper- and hypothyroidism show a reduction in basal NO synthesis/release, this reduced systemic NO tone being essential for life in hyperthyroid rats; whereas the response to ACh is not reduced and the hypotensive response to SNP did not differ between groups, indicating that the responsiveness of the systemic circulation to NO is not altered in either thyroid disorder.
Gen Pharmacol 1994 Sep
PMID:Role of nitric oxide in the systemic circulation of conscious hyper- and hypothyroid rats. 783 32

1. The present study was undertaken to determine whether endothelial nitric oxide (NO) is involved in the endothelium-dependent vasodilation elicited by bradykinin (BK) in rings of newborn (1-7-day-old) piglet cerebral arteries precontracted with KCl (25 mM). 2. In these rings, BK (10(-10)-10(-6) M) induced concentration-dependent relaxation. The preincubation with the precursor of NO synthesis, L-arginine (10(-4) M), reduced KCl-induced contraction and increased the BK relaxation. However, preincubation with the NO synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME; 3 x 10(-5) M), increased KCl contraction and basal tone, and inhibited BK relaxation. 3. These results suggest that the endothelium of these arteries possesses the ability to produce NO, either basal or stimulated by agents like BK.
Gen Pharmacol 1994 Sep
PMID:Role of nitric oxide on the endothelium-dependent vasodilation in newborn piglet cerebral arteries. 783 34

1. The present study has evaluated the effect of iosorbide 5-mononitrate (IS-5-MN) and L-arginine on blood pressure profile during chronic administration of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). 2. After a 7 day period of stabilization, normotensive male Wistar rats (n = 10) were selected and given L-NAME (50 micrograms/ml) in drinking water. Control rats (n = 10) were studied simultaneously for direct comparison of cardiovascular parameters. Blood pressure (systolic, SBP; diastolic, DBP) and heart rate were measured using a photoelectric tail cuff pulse detector; SBP and DBP were, in normotensive rats 106 +/- 2 and 78 +/- 2 mmHg (n = 10), respectively. The average water consumption per animal was about 35 ml/day resulting in a mean intake of L-NAME of about 10 mg/kg/day. 3. Twenty four hours after exposure to L-NAME, both SBP and DBP were found to be increased by 20 mm Hg; heart rate slightly decreased. During the next 13 days both SBP and DBP increased progressively reaching 170 +/- 3 and 116 +/- 3 mm Hg, respectively. 4. On day 14, six animals of either group were sacrificed and the heart, kidneys, liver, spleen, mesenteric and caudal arteries, brain stem, hypothalamus and parietal cortex were taken from determination of noradrenaline and dopamine content; blood from the renal vein was also collected and plasma concentrations of noradrenaline, adrenaline and 3,4-dihydroxyphenylethylglycol (DOPEG) determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Gen Pharmacol 1994 Nov
PMID:Isosorbide 5-mononitrate reverses high blood pressure in NG-nitro-L-arginine methyl ester treated rats. 789 42


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