Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analytical ultracentrifugation of highly purified seminalplasmin revealed a molecular mass of 6300. Amino acid analysis of the protein preparation indicated the absence of sulfur-containing amino acids cysteine and methionine. The amino acid sequence of seminalplasmin was determined by manual Edman degradation of peptides obtained by proteolytic enzymes trypsin, chymotrypsin and thermolysin: NH(2)-Ser Asp Glu Lys Ala Ser Pro Asp Lys His His Arg Phe Ser Leu Ser Arg Tyr Ala Lys Leu Ala Asn Arg Leu Ser Lys Trp Ile Gly Asn Arg Gly Asn Arg Leu Ala Asn Pro Lys Leu Leu Glu Thr Phe Lys Ser Val-COOH. The number of amino acids according to the sequence were 48, the molecular mass 6385. As predicted from the sequence, seminalplasmin very likely contains two alpha-helical domains in which residues 8-17 and 40-48 are involved. No evidence for the existence of beta-sheet structures was obtained. Treatment of seminalplasmin with the above proteases as well as with amino peptidase M and carboxypeptidase Y completely eliminated biological activity.
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PMID:Amino acid sequence of seminalplasmin, an antimicrobial protein from bull semen. 1645 69

We have previously shown in rats that lipopolysaccharide (LPS) causes both decreased renal perfusion and kidney arginine production before nitric oxide (NO) synthesis, resulting in a >30% reduction in plasma arginine. To clarify the early phase effects of LPS, we asked the following two questions: 1) is the rapid change in renal arginine production after LPS simply the result of decreased substrate (i.e., citrulline) delivery to the kidney or due to impaired uptake and conversion and 2) is the systemic production of NO limited by plasma arginine availability after LPS? Arterial and renal vein plasma was sampled at 30-min intervals from anesthetized rats with or without citrulline or arginine (2 micromol.min(-1).kg(-1) iv) a dose with no effect on MAP, renal function, or NO production. Exogenous citrulline was quickly converted to arginine by the kidney, resulting in plasma levels similar to equimolar arginine infusion. Also, the increase in citrulline uptake resulted primarily from increased filtered load and reabsorption. In a separate series, citrulline was infused after LPS administration, verifying that citrulline uptake and conversion persists during impaired kidney function. Last, in rats given LPS, the elevation of plasma arginine had no discernable impact on mean arterial pressure, kidney function, or systemic NO production. This work demonstrates how arginine synthesis is normally "substrate limited" and explains how impaired kidney perfusion quickly results in decreased plasma arginine. However, contrary to in vitro studies, the significant reduction in extracellular arginine during the early phase response to LPS in vivo is not functionally rate limiting for NO production.
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PMID:Acute renal response to LPS: impaired arginine production and inducible nitric oxide synthase activity. 1661 48

Hypertonic saline solutions improve cerebral blood flow (CBF) when used for acute resuscitation from hemorrhagic hypotension accompanying some models of traumatic brain injury (TBI); however, the duration of increased CBF is brief. Because the nitric oxide synthase substrate l-arginine provides prolonged improvement in CBF after TBI, we investigated whether a hypertonic resuscitation fluid containing l-arginine would improve CBF in comparison to hypertonic saline without l-arginine in a model of moderate, paramedian, fluid-percussion TBI followed immediately by hemorrhagic hypotension (mean arterial pressure [MAP] = 60 mm Hg for 45 min). Sprague-Dawley rats were anesthetized with 4.0% isoflurane, intubated and ventilated with 1.5%-2.0% isoflurane in oxygen/air (50:50). After preparation for TBI and measurement of CBF using laser Doppler flowmetry and measurement of intracranial pressure (ICP) using an implanted transducer, rats were subjected to moderate (2.0 atm) TBI, hemorrhaged for 45 min, and randomly assigned to receive an infusion of hypertonic saline (7.5%, 2,400 mOsm total; 6 mL/kg; n = 6) or hypertonic saline with 50, 100, or 300 mg/kg L-arginine (2,400 mOsm; 6 mL/kg; n = 6 in each of the three dose groups) and then monitored for 120 min after the end of infusion. CBF was measured continuously and calculated as a percent of the pre-TBI baseline during the hemorrhage period, after reinfusion of one of the hypertonic arginine solutions, and 30, 60, and 120 min after reinfusion. All four hypertonic solutions initially improved MAP, which, by 120 min after infusion, had decreased nearly to the levels observed during hemorrhage. ICP remained below baseline levels during resuscitation in all groups, although ICP was slightly greater (P = NS) than baseline in the hypertonic saline group. CBF increased similarly in all groups during infusion and then decreased similarly in all groups. At 120 min after infusion, CBF was highest in the group infused with hypertonic saline, but the difference was not significant. We conclude that the improvement of MAP, ICP, and CBF produced by hypertonic saline alone after TBI and hemorrhagic hypotension is not significantly enhanced by the addition of L-arginine at these doses.
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PMID:Effects of hypertonic arginine on cerebral blood flow and intracranial pressure after traumatic brain injury combined with hemorrhagic hypotension. 1691 55

Increased blood pressure induces functional and structural changes of the vascular endothelium. Depression of endothelium-dependant vasodilatation is an early manifestation of endothelial dysfunction due to hypertension. It can be demonstrated by pharmacological or physiological tests. Decreased availability of nitric oxide (NO) is a major determinant of the depression of vasodilatation. It may be caused by a reduction in the activity of NO-endothelial synthase (NOSe) related to: 1) a deficit in substrate (L-arginine), 2) an inhibition by asymmetrical dimethylarginine, 3) a deficit in the cofactor tetrahydrobiopterin (BH4). However, the increase in oxidative stress, a producer of superoxide radicals which combine with NO to form peroxynitrates (ONOO-), is the determining factor. It is related to activation of membranous NAD(P)H oxidases initiated by the stimulation of activating mecanosensors of protein C kinase. The message is amplified by oxidation of BH4 which transforms the NOSe into a producer of superoxide radicals. A cascade of auto-amplification loops leading to atherosclerosis and its complications is then triggered. The superoxide radicals and the peroxynitrates oxidise the LDL-cholesterol. They activate the nuclear factor-kappaB which controls the genes stimulating the expression of many proteins: angiotensinogen and AT1 receptors which stimulate the sympathetic system, receptors of oxidised LDL, adhesion and migration factors (ICAM-1, VCAM-1, E-selectin and MCP-1), pro-inflammatory cytokins (interleukines and TNF-alpha), growth factors (MAP kinases), plasminogen activator inhibitor 1. The monocytes and smooth muscle cells produce metalloproteinases and pro-inflammatory cytokins which destabilise the atheromatous plaque and favourise vascular remodelling. Inshort, the endothelial dysfunction due to hypertension plays a role in a complex physiopathological process and is a marker of future cardiovascular events.
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PMID:[Hypertension, endothelial dysfunction and cardiovascular risk]. 1710 Jan 43

We have studied the effects of L-NG-nitro arginine methyl esther (L-NAME), L-arginine (LAR), inhibitor and a donating nitric oxide agent on the alterations of salivary flow, water intake, arterial blood pressure (MAP) and heart rate (HR) induced by the injection pilocarpine into the subfornical organ (SFO). Rats (Holtzman 250-300 g) were anesthetized with 2, 2, 2-tribromoethanol (20 mg/100 kg b. wt.) and a stainless steel cannula were implanted into their SFO. The volume of injection was 0.2 microl. The amount of saliva secretion was studied over a 5-min period. Pilocarpine (40 microg), L-NAME (40 microg) and LAR (30 microg) were used in all experiments for the injection into the SFO. Pilocarpine (10, 20, 40, 80 and 160 microg) injected into SFO elicited a concentration-dependent increase in salivary secretion. L-NAME injected prior to pilocarpine into the SFO increased salivary secretion and water intake due to the effect of pilocarpine. LAR injected prior to pilocarpine into the SFO attenuated the salivary secretion and water intake. Pilocarpine, injected into the SFO increased the MAP and decreased heart rate (HR). L-NAME injected prior to pilocarpine into the SFO potentiated the pressor effect of pilocarpine with a decrease in HR. LAR injected into the SFO prior to pilocarpine attenuated the increase in MAP with no changes in HR. The present study suggests that the SFO nitrergic cells interfere in the cholinergic pathways implicated in the control of salivary secretion, fluid and cardiovascular homeostasis.
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PMID:Functional relationship between subfornical organ cholinergic stimulation and nitrergic activation influencing cardiovascular and body fluid homeostasis. 1739 80

Protein arginine methylation often modulates protein-protein interactions. To isolate a sufficient quantity of proteins enriched in methyl arginine(s) from natural sources for biochemical studies is laborious and difficult. We describe here an expression system that produces recombinant proteins that are enriched in omega-N(G),N(G)-asymmetry dimethylarginines. A yeast type I arginine methyltransferase gene (HMT1) is put on a plasmid under the control of the Escherichia coli methionine aminopeptidase promoter for constitutive expression. The protein targeted for post-translational modification is put on the same plasmid behind a T7 promoter for inducible expression of His(6)-tagged proteins. Sbp1p and Stm1p were used as model proteins to examine this expression system. The 13 arginines within the arginine-glycine-rich motif of Sbp1p and the RGG sequence near the C terminus of Stm1p were methylated. Unexpectedly, the arginine residue on the thrombin cleavage site (LVPRGS) of the fusion proteins can also be methylated by Hmt1p. Sbp1p and Sbp1p/hmt1 were covalently attached to solid supports for the isolation of interacting proteins. The results indicate that arginine methylation on Sbp1p exerts both positive and negative effects on protein-protein interaction.
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PMID:Expression of proteins with dimethylarginines in Escherichia coli for protein-protein interaction studies. 1745 44

Cerebrovascular dysfunction ensuing from severe heatstroke includes intracranial hypertension, cerebral hypoperfusion, and brain inflammation. We attempted to assess whether L-arginine improves survival during experimental heatstroke by attenuating these reactions. Anesthetized rats, 70 min after the start of heat stress (43 degrees C), were divided into two major groups and given the following: vehicle solution (1 mL/kg body weight) or L-arginine (50-250 mg/kg body weight) intravenously. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat stress, their survival time values were found to be 20 to 26 min. Treatment with i.v. doses of L-arginine significantly improved the survival rate during heatstroke (54-245 min). As compared with those of normothermic controls, all vehicle-treated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in hypothalamus. In addition, hypothalamic levels of IL-1beta and TNF-alpha were elevated after heatstroke onset. In contrast, all vehicle-treated heatstroke animals had lower levels of MAP, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of oxygen. Administration of L-arginine immediately after the onset of heatstroke significantly reduced the intracranial hypertension and the increased levels of NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in the hypothalamus were suppressed by L-arginine treatment. In contrast, the hypothalamic levels of IL-10 were significantly elevated by L-arginine during heatstroke. The results suggest that L-arginine may cause attenuation of heatstroke by reducing cerebrovascular dysfunction and brain inflammation.
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PMID:L-arginine causes amelioration of cerebrovascular dysfunction and brain inflammation during experimental heatstroke. 1769 25

Experimental hypertension studies are few in the hooded (Aguti) rat. The present study was designed to investigate the usefulness of this rat strain for experimental hypertension studies and to test the hypothesis that the hypertension may be associated with a diminution of endothelium dependent and independent relaxations. Hypertension was induced in inbred hooded rats (n=8 each) by administering 8% salt in the diet and /or 100 mg/kg/day Nomega-nitro-L-arginine-methyl-ester (L-NAME) in the drinking water for six and/or four weeks respectively. The rats were anaesthetized using a 25% urethane and 1% chloralose mixture given intraperitoneally at a dose of 5 mg/kg. Their blood pressure was measured invasively. Thereafter, relaxations of rat aortic preparations to acetylcholine, histamine and sodium nitroprusside (SNP) were assessed using standard organ bath conditions. Probability level of 0.05 was taken as statistically significant. The mean arterial pressure (MAP;mm Hg) rose significantly in all test groups (Salt: 148.3 +/- 4.6; L-NAME: 181.7 +/-8.3; Salt+L-NAME:154.9 +/-8.7) compared with control (94.2 +/-6.8; [P < 0.05]. The MAP was significantly [P < 0.05] higher in the L-NAME group than in all the other groups. The heart rate fell significantly in the salt + L-NAME group compared to control [P <0.05].The IC50 of acetylcholine in aortic rings from L-NAME rats (7.9 x 10(-1) +/- 6.0 x 10(-3)) was significantly higher than in rings from control (9.4 x 10(-8) +/- 2.8 x 10(-8)), salt (7.8 x 10(-7) +/- 4.7 x 10(-7)) and salt + L-NAME (3.3 x 10 (-7) +/- 2.1 x 10(-7)) rats [P < 0.05]. The IC50 of histamine and SNP in the rings from the test groups of rats showed no significant difference from control. Also, endothelium dependent and independent relaxations were preserved in the various forms of hypertension studied except in chronic NOS inhibition where the former was attenuated in response to acetylcholine.
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PMID:Endothelum-dependent and-independent relaxations in aortic rings obtained from hypertensive hooded (Aguti) rats. 1837 29

The roles of NO and isozymes of NO synthase (NOS) are not known in anaphylactic hypotension of unanesthetized rats. Effects of inhibition of NOS, iNOS, and nNOS by N-nitro-L-arginine methyl ester (L-NAME), aminoguanidine, and 7-nitroindazole, respectively, were determined on the antigen-induced systemic hypotension and portal hypertension in conscious Sprague-Dawley rats sensitized with the ovalbumin antigen. The MAP and portal venous pressure were directly and simultaneously measured. The control rats showed a decrease in MAP along with an increase in portal venous pressure but did not die within 48 h after antigen injection. In the rats pretreated with the nonselective NOS inhibitor L-NAME (10 mg/kg), MAP before and after antigen administration was significantly higher than that of the control rats, but the net decrease in MAP and increase in portal venous pressure were rather greater than those of the control, resulting in fatal outcome within 12 h after antigen administration. In contrast, pretreatment with the relatively selective nNOS inhibitor 7-nitroindazole (50 mg/kg) substantially attenuated anaphylactic hypotension over 20 min after antigen administration, whereas the relatively selective iNOS inhibitor aminoguanidine (100 mg/kg) did not affect it. In conclusion, in anaphylactic hypotension of unanesthetized rats, NO derived from nNOS, but not from iNOS, may be involved, and the nonselective NOS inhibitor L-NAME is lethal.
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PMID:7-nitroindazole, but not L-NAME or aminoguanidine, attenuates anaphylactic hypotension in conscious rats. 1849 3

Both short-term and long-term nitric oxide (NO) blockade were shown to cause an increase in O(2)(-) activity. To assess the contribution of such enhanced O(2)(-) activity in the kidney, responses to administration of the NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME; 200 microg.min(-1).kg body wt(-1)) were assessed in knockout mice the lacking NAD(P)H oxidase subunit gp91(phox) (KO; n = 10) and in wild-type (WT; n = 10) mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearances, respectively. Baseline RBF was higher in KO compared with WT mice (5.8 +/- 0.5 vs. 4.5 +/- 0.3 ml.min(-1).g(-1); P < 0.04) without significant differences in GFR (0.62 +/- 0.04 vs. 0.73 +/- 0.05 ml.min(-1).g(-1)) and in mean arterial pressure (MAP; 91 +/- 6 vs. 88 +/- 4 mmHg). L-NAME infusion for 60 min caused similar increases in MAP (114 +/- 6 vs. 113 +/- 3 mmHg) in both groups but resulted in a lesser degree of reduction in RBF in KO compared with WT mice (-7 +/- 3 vs. -17 +/- 3%; P < 0.02), although GFR remained unchanged in both groups. The natriuretic response to systemic L-NAME infusion was attenuated in KO compared with WT mice (Delta: 3.1 +/- 0.7 vs. 5.2 +/- 0.6 micromol.min(-1).g(-1)). L-NAME increased urinary 8-isoprostane excretion rate in WT (5.9 +/- 1 to 7.7 +/- 1 pg.min(-1).g(-1); P < 0.02) but not in KO mice (5.6 +/- 1 to 4.9 +/- 0.3 pg.min(-1).g(-1)). In contrast, responses to another vasoconstrictor, norepinephrine, were similar in both strains of mice. These data indicate that activation of NAD(P)H oxidase results in the enhancement of O(2)(-) activity that influences renal hemodynamics and excretory function in the condition of NO deficiency.
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PMID:Reduced renal responses to nitric oxide synthase inhibition in mice lacking the gene for gp91phox subunit of NAD(P)H oxidase. 1859 78


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