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

The mechanisms that regulate mucin release in chronic otitis media with effusion, a leading cause of hearing loss in children, remain largely unknown. We developed an animal model using Sprague-Dawley rats to determine the factors responsible for mucin production in chronic otitis media with effusion. N-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, was used to investigate the role of nitric oxide in mucin secretion by the middle ear epithelium. All rats underwent eustachian tube obstruction. In the first set of rats, the middle ear was then injected transtympanically with 35 microl of either 300 mOsm Krebs-Ringer bicarbonate buffer (control group) or 1 mg/ml lipopolysaccharide in Krebs-Ringer (experimental group 1). In a second set of rats, the middle ear space was injected with lipopolysaccharide and then infused at a continuous rate for 7 days with either Krebs-Ringer (experimental group 2) or 1 mmol/L L-NAME in Krebs-Ringer (experimental group 3) through an osmotic infusion pump. After 7 days the volume of effusion and the quantity of mucin collected were significantly greater in lipopolysaccharide-exposed ears than in controls. In addition, antimucin immunostaining demonstrated mucous cell hyperplasia in response to lipopolysaccharide. The lipopolysaccharide-induced production of mucin and mucous cell hyperplasia was inhibited in ears treated with lipopolysaccharide and L-NAME. These results suggest that nitric oxide is a mediator in the pathway of mucin secretion in chronic otitis media with effusion.
 ...
PMID:Nitric oxide mediates mucin secretion in endotoxin-induced otitis media with effusion. 912 82

The production of nasal fluids serves an important role in the protection of the upper respiratory system, but can also be a troublesome symptom of rhinitis. The chief sources of nasal fluids are serous and mucous glandular secretion, epithelial goblet cell exocytosis, and exudation from submucosal blood vessels. This study was designed to investigate the role of nitric oxide in neurogenically mediated nasal vascular exudation and mucus secretion. A rat model of the naso-nasal reflex was developed in which one nasal cavity was challenged with histamine while albumin and mucin production were measured in the continuously perfused contralateral side. Histamine challenge was associated with a significant rise in contralateral albumin and mucin content. Perfusion with a nitric oxide synthase inhibitor (L-NAME) in the nasal cavity contralateral to nasal challenge was found to block albumin leakage, but not mucin secretion, on that side. The inhibition of vascular exudation was overcome by the addition of L-arginine, the natural substrate of nitric oxide synthase, to the perfusate. Treatment of the ipsilateral nasal of the ipsilateral nasal cavity with L-NAME did not significantly after the contralateral response. A high correlation was observed between albumin and mucin concentration in the perfusate. These findings indicate that NO is a mediator of the effector arm of the naso-nasal reflex that increases vascular permeability, but is not involved in the sensory nerve afferent pathway or in reflex mucin release. Further elucidation of the role of NO in nasal physiology may lead to novel pharmacotherapeutic approaches to the treatment of allergic and non-allergic rhinitis.
 ...
PMID:The role of nitric oxide in the neural control of nasal fluid production. 934 Jan 98

Biliary infection is associated with mucin hypersecretion by the biliary epithelium. Mucins have been identified as potent pronucleators of cholesterol in bile. The aim of the present study was to determine whether lipopolysaccharides (LPS) from different bacteria are capable of stimulating mucin secretion by cultured dog gallbladder epithelial (DGBE) cells, and to investigate the mechanism by which LPS stimulate mucin secretion. Mucin secretion by confluent monolayers of DGBE cells was quantified by measuring the secretion of [3H]-N-acetyl-D-glucosamine-labeled glycoproteins. Cell viability was evaluated by measuring the leakage of the enzyme, lactate dehydrogenase (LDH), into the culture medium. LPS, derived from Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa (200 microg/mL), all caused an increase in mucin secretion by the DGBE cells, without causing concomitant cell lysis. LPS from E. coli was found to be the most potent stimulator of mucin secretion, and increased mucin secretion by the DGBE cells to 252% +/- 14% of control. LPS from E. coli had no effect on intracellular cyclic adenosine monophosphate (cAMP) levels in the DGBE cells. Addition of the nitric oxide (NO)-releasing compound, NOR-4 (0.125-1 mmol/L), to the cells did not result in increased mucin secretion, and the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME) (4 or 10 mmol/L), did not inhibit the LPS-stimulated mucin secretion. Exogenous tumor necrosis factor alpha (TNF-alpha) (1-10 ng/mL) did cause a minor increase in mucin secretion by the DGBE cells, but the effect of LPS from E. coli on mucin secretion could not be inhibited by preincubation with a TNF-alpha antibody (10 microg/mL). We conclude that LPS stimulates mucin secretion by the gallbladder epithelium. Whether this stimulation is mediated by TNF-alpha remains to be determined.
 ...
PMID:Lipopolysaccharide from Escherichia coli stimulates mucin secretion by cultured dog gallbladder epithelial cells. 1021 15

Gastric ulceration was induced in rats by i.p. injection of the non-steroidal anti-inflammatory drug (NSAID), indomethacin (IND) (30 mg kg(-1)). Pyloric ligation was carried out in each animal before injection to enable collection of the gastric juice. Three hours later, the animals were killed and their stomachs were removed. In the gastric juice, the amounts of mucin, pepsin and HCl were assessed. Gastric mucosa were scrapped for the determination of nitric oxide (NO) (as nitrite) after evaluation of the gastric ulcer index. The influence of arginine (ARG) (300 mg kg(-1)), a NO precursor, N(G)-nitro- l -arginine methyl ester (l -NAME) (50 mg kg(-1)), a non-selective constitutive nitric oxide synthase/inducible nitric oxide synthase (cNOS/iNOS) inhibitor, and the selective iNOS inhibitor aminoguanidine (AMG) (50 mg kg(-1)) were studied. Each NO modulator was injected i.p. 30 min before IND administration. Results indicated that IND elevated gastric acidity by 80% of the normal group, decreased non-significantly mucosal nitrite by 22% and exhibited a remarkably high ulcer index (chi = 17). Neither mucin nor pepsin levels were significantly altered. In comparison with the IND group, pretreatment with l -NAME caused a significant decrease in gastric HCl, further decrease in mucosal nitrite (50% of normal) and a two-fold increase in the ulcer index score (chi = 34), despite the decrease in HCl. AMG did not alter gastric acidity, decreased mucosal nitrite by 38% of the normal value and failed to alter significantly the ulcer index of IND. On the other hand, pretreatment with ARG did not alter the gastric acidity and raised mucosal nitrite by 10% above normal. Surprisingly, ARG improved the gastric ulcer score (chi = 1) almost similar to the normal score (chi = zero). Therefore, this study creates a new pathway for the potential treatment of NSAID gastric ulceration through modulation of NO synthesis, regardless of the effect on gastric acidity.
 ...
PMID:Protective role of nitric oxide in indomethacin-induced gastric ulceration by a mechanism independent of gastric acid secretion. 1139 38

The aim of this study was to investigate the effect of N-G-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase inhibitor, on the gastric mucosal barrier in rats. A group of Swiss albino rats received L-NAME (60 mg/kg/d) in their drinking water daily for 21 d. The mucin and prostaglandin E2 (PGE2) contents of the gastric mucosa were measured in gastric tissue samples. L-NAME intake did not affect gastric mucin, but it significantly reduced PGE2, a component of the gastric mucosal barrier. The results of this study imply that nitric oxide plays an important mediatory role in maintaining the gastric mucosal barrier. The inhibition of nitric oxide may be involved in the increased vulnerability of the gastric mucosa to injurious stimuli in rats.
 ...
PMID:Effect of nitric oxide synthase inhibition on the gastric mucosal barrier in rats. 1176 95

Porphyromonas gingivalis is a Gram-negative periodontopathic bacterium colonizing the oral cavity and its lipopolysaccharide (LPS) is a key factor in the development of periodontitis. We investigated the effect of P. gingivalis LPS on the cellular responses associated with mucin synthesis in sublingual salivary gland acinar cells. Exposure of the acinar cells to the LPS led to a dose-dependent decrease in mucin synthesis and was accompanied by a massive induction in inducible nitric oxide synthase (NOS-2) activity and the increase in NO production, caspase-3 activity and apoptosis. Inhibition of extracellular signal-regulated kinase (ERK) with PD98059 accelerated the LPS-induced decrease in the glycoprotein synthesis and caused further increase in apoptosis and NOS-2 activity, while the blockade of p38 mitogen-activated kinase (MAPK) with SB203580 countered the LPS-induced reduction in the glycoprotein synthesis and obviated the induced increases in NOS-2 and apoptosis. Introduction of NOS-2 inhibitor, L-NAME, not only countered the LPS-induced increase in NO generation, caspase-3 activity and apoptosis, but caused the impedance of the LPS inhibition on mucin synthesis. The findings point to the upregulation in NOS-2 expression by P. gingivalis LPS as a key detrimental culprit affecting salivary mucin synthesis.
 ...
PMID:Porphyromonas gingivalis lipopolysaccharide interferes with salivary mucin synthesis through inducible nitric oxide synthase activation by ERK and p38 kinase. 1237 6

We have investigated the vascular relaxant effects of the lectin from a red marine alga Bryothamnion triquetrum (BTL), in particular, the endothelial-dependency and the participation of a specific glycoprotein-binding site. BTL (1-100 microg mL(-1)) was applied to rat isolated aortic rings, with or without endothelium, tonically precontracted with phenylephrine (0.1 microM). Endothelium-dependent relaxation was assessed in the presence of indometacin (10 microM), L-nitro arginine methyl ester (L-NAME, 100 microM) and tetraethylammonium (TEA, 500 microM). For the involvement of the glycoprotein-binding site, BTL was assayed in presence of mucin (300 microg mL(-1)) or N-acetyl D-glucosamine (GlcNAc; 300 microg mL(-1)), a specific and non-specific lectin-binding sugar, respectively. BTL fully and concentration dependently relaxed preparations that possessed an intact endothelium (IC50 (concn producing 50% contraction) = 12.1 +/- 1.6 microg mL(-1)), whereas no significant relaxation was observed in endothelial-denuded tissue. L-NAME, but not indometacin or TEA, completely inhibited the lectin relaxation, suggesting the involvement of nitric oxide (NO). The lectin in association with mucin, but not with GlcNAc, inhibited BTL-induced relaxation, implicating the involvement of the lectin binding site. Our data suggest that the relaxant effect of the red marine alga Bryothamnion triquetrumlectin on isolated aorta occurs via interaction with a specific lectin-binding site on the endothelium, resulting in a release of NO.
 ...
PMID:Red marine alga Bryothamnion triquetrum lectin induces endothelium-dependent relaxation of the rat aorta via release of nitric oxide. 1552 48

Inefficient adenoviral vector (AdV)-mediated gene transfer to the ciliated respiratory epithelium has hindered gene transfer strategies for the treatment of cystic fibrosis lung disease. In part, the inefficiency is due to an absence of the coxsackie B and adenovirus type 2 and 5 receptor (CAR) from the apical membranes of polarized epithelia. In this study, using an in vitro model of human ciliated airway epithelium, we show that providing a glycosylphosphatidylinositol (GPI)-linked AdV receptor (GPI-CAR) at the apical surface did not significantly improve AdV gene transfer efficiency because the lumenal surface glycocalyx limited the access of AdV to apical GPI-CAR. The highly glycosylated tethered mucins were considered to be significant glycocalyx components that restricted AdV access because proteolytic digestion and inhibitors of O-linked glycosylation enhanced AdV gene transfer. To determine whether these in vitro observations are relevant to the in vivo situation, we generated transgenic mice expressing GPI-CAR at the surface of the airway epithelium, crossbred these mice with mice that were genetically devoid of tethered mucin type 1 (Muc1), and tested the efficiency of gene transfer to murine airways expressing apical GPI-human CAR (GPI-hCAR) in the presence and absence of Muc1. We determined that AdV gene transfer to the murine airway epithelium was inefficient even in GPI-hCAR transgenic mice but that the gene transfer efficiency improved in the absence of Muc1. However, the inability to achieve a high gene transfer efficiency, even in mice with a deletion of Muc1, suggested that other glycocalyx components, possibly other tethered mucin types, also provide a significant barrier to AdV interacting with the airway lumenal surface.
 ...
PMID:Glycocalyx restricts adenoviral vector access to apical receptors expressed on respiratory epithelium in vitro and in vivo: role for tethered mucins as barriers to lumenal infection. 1556 84

This study investigated the possible mechanisms underlying the gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats. Rats were randomly assigned to vehicle-, simvastatin-, simvastatin+L-arginine- and simvastatin+N(G)-nitro-L-arginine methyl ester (L-NAME)-pretreated groups for two weeks. Pyloric ligation was performed for the collection of gastric juice, and gastric ulceration was induced by a single intraperitoneal injection of indomethacin (30 mg/kg). Gastric juice parameters (total acid output, pepsin activity and mucin concentration) were determined. The stomachs tissues were used for determination of gastric mucosal lipid peroxides, superoxide dismutase, catalase, total nitrites and prostaglandin E(2) levels. Pretreatment with simvastatin (10 mg/kg, orally, for 2 weeks) caused significant reduction in gastric mucosal lesions and lipid peroxides associated with a significant increase in gastric juice mucin concentration. Simvastatin significantly increased the gastric mucosal total nitrite and prostaglandin E(2) levels. Additionally, simvastatin attenuated the elevations in gastric mucosal superoxide dismutase observed with indomethacin. The gastroprotective effect afforded by simvastatin was significantly augmented by coadministration with L-arginine (a nitric oxide precursor) and inhibited by coadministration with L-NAME (a nitric oxide synthase inhibitor). Results confirm a gastroprotective effect for simvastatin, and indicate that the anti-ulcer effect of simvastatin is mediated by scavenging free radicals, increasing nitric oxide and prostaglandin E(2) levels, and increasing gastric juice mucin production. We conclude that simvastatin represents a more suitable antihyperlipidemic therapy for patients who are at risk of gastric ulcers that were induced by the use of nonsteroidal anti-inflammatory drugs (NSAIDs).
 ...
PMID:Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: role of nitric oxide and prostaglandins. 1921 1

Bryothamnion seaforthii lectin (BSL) induced reversible concentration-related relaxation of endothelized aorta, maximal at 30 microg/ml (IC(50)= 4.8 +/- 0.6 microg/ml). This effect was inhibited by L-NAME and reversed by mucin, probably via interaction with a specific lectin-binding site on the endothelium activating nitric oxide synthase.
 ...
PMID:Bryothamnion seaforthii lectin relaxes vascular smooth muscle: involvement of endothelium and NO synthase. 2023 85


<< Previous 1 2 3 Next >>