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Biomedical subjects

V L Murty

Publications and source records attributed to V L Murty.

At least 19 recordsLinked to original sources
PubMed1996

Salivary mucins in oral mucosal defense.

1. Salivary mucins are well recognized as an important factor in the preservation of the health of the oral cavity. These large glycoproteins play a major role in the formation of protective coatings covering tooth enamel and oral mucosa, which act as a dynamic functional barrier capable of modulating the untoward effects of oral environment, and are of significance to the processes occurring within the epithelial perimeter of mucosal defense. 2. Based on macromolecular characteristics, the mucins in saliva fall into high (> 1000 kDa) and low (200-300 kDa) molecular weight forms. The two forms, although differ with respect to bacterial clearance ability, display virtually identical carbohydrate chain make-up, ranging in size from 3 to 16 sugar units. 3. Of the two mucin forms, the low molecular weight form more efficient in bacterial aggregation, predominates in saliva and oral mucosal mucus coat of caries-resistant individuals, while the level of the high molecular weight form is higher in caries-susceptible subjects. The saliva of caries-resistant individuals also exhibits greater activity of protease capable of conversion of the high molecular weight mucin to the low molecular weight form. 4. The bacterial aggregating activity of salivary mucins appears to be associated with sulfomucins rather than sialomucins. While the removal of sialic acid causes only partial loss in mucin aggregating capacity, a complete loss in the bacterial aggregating activity occurs following mucin desulfation. 5. The mucins in oral mucosal mucus coat interact with the epithelial surfaces through specific membrane receptors. This interaction apparently involves the carbohydrate moiety of mucin molecule and may be rendered vulnerable to disruption by opportunistic bacteria colonizing the oral mucosa. 6. Salivary sulfo- and sialomucins actively participate in the modulation of the oral mucosal calcium channel activity through the inhibition of EGF-stimulated channel protein tyrosine phosphorylation. This function of salivary mucins is of paramount importance to mucosal calcium homeostasis.

Animals↗
PubMed1995

Enhancement in gastric mucosal EGF and PDGF receptor expression with ulcer healing by sulglycotide.

1. The effect of an antiulcer agent, sulglycotide, on mucosal expression of EGF and PDGF receptors with chronic ulcer healing was investigated. 2. Rats with experimentally-induced gastric ulcers were treated twice daily for 14 consecutive days, either with sulglycotide at 200 mg/kg or vehicle, and at different stages of treatment used for quantitation of gastric mucosal EGF and PDGF receptors. 3. The ulcer healing was accompanied by an increase in mucosal expression of both types of receptors. A 1.8-fold increase in EGF and 3.1-fold increase in PDGF receptors occurred by the 4th day following the development of ulcer and reached a maximum of 2.4-3.9-fold increase by the 10-14th day. 4. Treatment with sulglycotide caused accelerated ulcer healing accompanied by a significant enhancement in the receptors expression. A 2.3- and 3.6-fold increase in EGF and PDGF receptor expression occurred by the 4th day of sulglycotide treatment, reaching a 5.5- and 5.6-fold respective increase by the 10th day when the ulcer essentially healed. 5. The results attest to the ability of sulglycotide to stimulate the gastric mucosal proliferative activities associated with ulcer healing.

Acetates↗
PubMed1995

Inhibition of gastric mucosal mucin receptor by H. pylori lipopolysaccharide: effect of ebrotidine.

1. H. pylori infection causes the loss of mucus coat continuity and its patchy appearance. Here, we present evidence that the bacterium, through its cell wall lipopolysaccharide, disrupts the interaction between mucin and its mucosal receptor, and that ebrotidine is capable of counteracting this process. 2. The receptor for mucin, isolated from the solubilized gastric epithelial cell membrane by affinity chromatography on Sepharose-bound wheat germ agglutinin, displayed a molecular weight of 97 kDa and exhibited specific affinity towards mucin-coated surface. 3. The mucin binding to the receptor was susceptible to the inhibitin by H. pylori lipopolysaccharide and reached a maximum of 91%. This effect of the lipopolysaccharide was counteracted by ebrotidine, which caused a dose-dependent relief of the lipopolysaccharide inhibitory effect with maximum restoration in mucin-receptor binding of 51% at 60 microliters/ml ebrotidine. 4. The results show that H. pylori, through its lipopolysaccharide, is capable of disrupting the integrity of mucus perimeter of gastric mucosal defense and that antiulcer agent, ebrotidine, counteracts this untoward effect.

Animals↗
PubMed1995

Susceptibility of Helicobacter pylori to antimicrobial agents: effect of sulglycotide.

H. pylori is regarded as a primary etiologic factor in gastric disease and the therapies now include a combination of antimicrobial agents with antiulcer drugs. Here, the effect of a new gastroprotective agent, sulglycotide, on the in vitro anti-H. pylori activity of metronidazole, erythromycin, tetracycline, and amoxycillin was assessed. The assays in the absence of sulglycotide gave MIC value 0.10mg/L for erythromycin, 0.12mg/L for amoxycillin, 0.15mg/L for tetracycline and 14mg/L for metronidazole, while sulglycotide alone gave MIC value of 20mg/L. The sulglycotide at its optimal dose (5mg/L) evoked a 4-fold enhancement in the MIC of amoxycillin, 5-fold in tetracycline, and 8.3-fold in erythromycin, while the MIC of metronidazole improved 3.5-fold at 10mg/L sulglycotide. The results point towards the advantage of combination therapy of sulglycotide and antibiotics for H. pylori eradication.

Amoxicillin↗
PubMed1994

Activation of arachidonoyl phospholipase A2 in prostaglandin-mediated action of sucralfate.

1. The mechanism of sucralfate-induced gastric mucosal prostaglandin generation was investigated using mucosal cells labeled with [14C]choline and [3H]arachidonic acid. 2. In comparison to the controls, the cells maintained in the presence of sucralfate showed a concentration dependent increase in lysophosphatidylcholine (LPC) synthesis and PGE2 generation. The maximal effect was attained at 25 microM sucralfate giving a 45.7% increase in LPC and 70% increase in PGE2. 3. Pretreatment with indomethacin prior to sucralfate, while causing inhibition in PGE2 generation, had no effect on LPC production and led to accumulation of free arachidonic acid. In the case of pretreatment with NDGA, the sucralfate caused increased LPC synthesis accompanied by enhanced PGE2 generation without free arachidonic acid accumulation. 4. The stimulatory effect of sucralfate on LPC synthesis and PGE2 generation was inhibited by phospholipase A2 inhibitors, mepacrine and BPB. The inhibitory effect was concentration dependent and attained maximum at 40 microM for BPB and 80 microM for mepacrine. 5. The results for the first time demonstrate that the enhancement in gastric mucosal prostaglandin generation by sucralfate results from the stimulation of mucosal phospholipase A2 for arachidonic acid release.

Animals↗
PubMed1994

Gastroprotective agents in mucosal defense against Helicobacter pylori.

1. Convincing evidence now exists that infection with H. pylori plays a major role in the pathogenesis of gastric disease. Having a niche bordering two major perimeters of mucosal defenses, the bacterium apparently exerts its detrimental effect on the mucus layer as well as the gastric epithelium. Therefore, gastroprotective agents capable of counteracting these detrimental effects of H. pylori are gaining importance in the treatment of gastric disease. 2. The colonization of gastric mucosa by H. pylori involves specific glycolipid receptors bearing acidic substituents, a process inhibited by gastric sulfomucins. Two antiulcer agents bearing sulfated sugar groups have been demonstrated to possess the ability to interfere with H. pylori colonization process. These are sucralfate and sulglycotide. The two agents are also potent inhibitors of H. pylori glycosulfatase activity directed against indigenous mucosal defenses. 3. A variety of extracellular enzymes such as proteases, lipases and phospholipases, elaborated by H. pylori cause the weakening of the integrity of gastric mucus coat and render the underlying epithelium vulnerable to noxious luminal contents. Among the most potent agents capable of countering the proteolytic activity of H. pylori are nitecapone, ebrotidine and sulglycotide, while ebrotidine and sulglycotide were found to be most effective inhibitors of H. pylori lipolytic activities. 4. The gastric epithelial integrity is compromized by the H. pylori cell-wall lipopolysaccharide untoward effect on the epithelial surface receptors. The interference of the lipopolysaccharide with the laminin receptor was found to be most efficiently countered by ebrotidine, sulglycotide and sucralfate, whereas sulglycotide is the most potent in the reversal of the inhibitory effect of the lipopolysaccharide on mucin receptor binding.

Animals↗
PubMed1994

Inhibition of gastric mucosal mucin receptor by Helicobacter pylori lipopolysaccharide: effect of sulglycotide.

1. A receptor for mucin was isolated from the solubilized gastric epithelial cell membrane by affinity chromatography on Sepharose-bound wheat germ agglutinin. 2. The receptor protein displayed a molecular weight of 97 kDa and exhibited specific affinity towards mucin-coated surfaces. The optimum for mucin binding occurred at 60-100 micrograms/ml, while the values for the receptor were 2.0-3.1 micrograms/ml. 3. The mucin binding to the receptor was susceptible to Helicobacter pylori lipopolysaccharide which caused maximum inhibition of 91% at 30 mu/ml. This inhibitory effect of the lipopolysaccharide was abolished by a gastroprotective agent, sulglycotide. 4. The effect of sulglycotide was dose dependent and at 50 micrograms/ml produced a 94% restoration in receptor-mucin binding. Furthermore, sulglycotide was also capable of enhancing (97%) the mucin binding to its receptor in the absence of the lipopolysaccharide. 5. The results demonstrate that H. pylori through its lipopolysaccharide interferes in the interaction of mucin with gastric epithelial surfaces and that a gastroprotective agent, sulglycotide, counteracts this effect, and hence is capable of preventing the loss of mucin coat continuity occurring with H. pylori infection.

Animals↗
PubMed1994

Enhancement of gastric mucus phospholipid secretion by an antiulcer agent, ebrotidine.

1. Rat gastric mucosal cells, subjected to phospholipid labeling by incubating the cell suspension in DMEM with [3H]choline, were exposed to different concentrations (0-150 microM) of H2-receptor antagonists, ebrotidine and ranitidine, and the phospholipid secretory responses were evaluated. 2. In the absence of the drugs, the secretion of choline-containing phospholipids over a 1 hr period averaged 3.97% of the total cellular labeled phospholipids. Ebrotidine caused a dose-dependent increase in the rate of phospholipid secretion which was most pronounced at 1 hr and persisted for at least 2 hr. The maximal effect was attained at 120 microM ebrotidine giving a 36% increase in phospholipid secretion. 3. The phospholipid secretory response to ebrotidine was accompanied by an increase in gastric mucosal cell cAMP level which reached a maximum value of 2.1-fold over that of controls at 1 hr. Ranitidine, in contrast, neither evoked increase in cAMP level nor caused any stimulation in phospholipid secretion. 4. The results indicate that the gastroprotective properties of ebrotidine are associated with the ability of the drug to elicit a rapid stimulation in gastric mucus phospholipid secretion, and that ranitidine does not possess such property.

Animals↗
PubMed1994

Helicobacter pylori aggregating activity of gastric mucin with ulcer healing by ebrotidine.

The mucin isolated from gastric secretion of duodenal ulcer patients before and after therapy with a new antiulcer agent, ebrotidine, was assessed for H. pylori aggregating activity and macromolecular organization. Analyses of mucin molecular forms revealed that successful therapy with ebrotidine was accompanied by a 2.6-2.9-fold increase in the high molecular weight mucin form. The H. pylori aggregation inhibition assays showed that therapy with ebrotidine evoked a 4-fold increase in mucin anti-H. pylori titer. The changes in the functional properties of mucin following ebrotidine therapy were also accompanied by a 36% increase in the content of sulfomucin. The results demonstrate that ulcer therapy with ebrotidine lead to a marked enhancement in mucin's qualities associated with maintenance of gastric mucosal integrity and strengthening the indigenous defenses against H. pylori.

Anti-Ulcer Agents↗
PubMed1994

Enhancement in gastric mucosal epidermal growth factor receptor expression by sulglycotide.

The effect of intragastric administration of sulglycotide, a cytoprotective sulfated glycopeptide, on the expression of gastric mucosal epidermal growth factor receptor was investigated. The experiments were conducted with groups of rats, one receiving twice daily for 5 consecutive days a dose of 200mg/kg sulglycotide, and the other only vehicle. Mucosal cell membranes were isolated from the stomachs at 16, 40 and 88h after the last dose, and used for EGF receptor assays. The binding assays revealed a marked increase in mucosal EGF receptor expression with sulglycotide. Compared to the controls, the sulglycotide-treated group showed a 4-fold increase in the EGF receptor expression at 16h after the last dose of sulglycotide, a 4.7-fold increase in the EGF receptor was observed by the 40h, and a 4.2-fold increase was still evident at 88h following the treatment. The results demonstrate that sulglycotide exhibits remarkable ability to enhance the gastric mucosal expression of EGF receptor.

Animals↗
PubMed1994

Association of salivary bacterial aggregating activity with sulfomucin.

The requirements of human salivary mucins for aggregating potential towards the common cariogenic oral bacteria, S. mutans and S. sanguis, were investigated. Agglutination inhibition assays demonstrated that the aggregating capacity towards bacteria resides in the acidic mucin fraction. The inhibitory activity of the acidic mucin decreased only 2-4-fold following removal of sialic acid, whereas the desulfation caused a complete loss of the inhibitory potential against both bacteria. Furthermore, the aggregating capacity of mucin-derived sulfated oligosaccharide was found to be 16-fold higher than that of the sialic acid containing oligosaccharide. The results point towards the importance of salivary sulfomucins as a predominant factor in the defense of oral cavity against cariogenic bacteria.

Adult↗
PubMed1993

Calcium transport and calcium activated ATPase activity in microsomal vesicles of rat gastric mucosa.

1. Microsomal and plasma membrane vesicles, isolated from rat gastric mucosa, were found to exhibit Ca(2+)-dependent ATPase activities of 14.1 +/- 1.4 and 7.8 +/- 1.1 mumol/mg/hr, respectively. The optimum conditions for the microsomal Ca(2+)-ATPase was pH 6-7, and required Mg2+, while divalent cation such as Cu2+, Zn2+, Fe2+, Ba2+ and Cd2+ had no significant effect. 2. As in the case of Ca2+, Mg(2+)-ATPase, the Ca2+ uptake activity of the microsomal membrane required Mg2+. Both processes were stimulated by submicro molar concentrations of Ca2+ and the apparent Km for Ca2+, Mg2+ ATPase and Ca2+ uptake activities were 0.06 microM and 0.02 microM, respectively. 3. Divalent cations Ba2+ and Fe2+, inhibited both microsomal activities, while Zn2+ and Cd2+ showed no effect on them. However, the monovalent cation K+ did not stimulate Ca2+, Mg(2+)-ATPase and Ca2+ uptake activities. 4. The Ca2+ pumping ATPase of rat gastric mucosal microsome cross-reacted with a monoclonal antibody (mAb-5F10) against the human erythrocyte Ca2+ pump. The apparent molecular weight of mucosal Ca2+ pump was 98 kDa. 5. Close relationship between the kinetic parameters of Ca2+, Mg(2+)-ATPase and Ca2+ uptake activities, and the cross reaction of 98 kDa protein of mucosal microsome with erythrocyte Ca2+ pump antibody, strongly suggest the expression of Ca2+ pump in rat gastric mucosa.

Animals↗
PubMed1993

Structural features of carbohydrate chains in human salivary mucins.

1. The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 2. Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 3. The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 4. Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. In two oligosaccharides sialic acid was linked to C3 of galactose and in one to C6 of N-acetylgalactosamine. The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine. 5. The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains.

ABO Blood-Group System↗
PubMed1993

Regulation of buccal mucosal calcium channel activity by salivary mucins.

1. The effect salivary mucins on the activity of calcium channel isolated from buccal mucosal cell membranes was investigated. The uptake of 45Ca2+ while only moderately (15%) affected by the intact low and high molecular weight mucin forms, was significantly inhibited, by the acidic low and high molecular weight salivary mucins which evoked 64 and 60% inhibition, respectively. 2. The inhibitory effect of salivary mucins was associated with the sialic acid and sulfate ester groups of the carbohydrate chains, as the removal of either group caused partial loss in the glycoproteins inhibition, and the complete loss in the inhibitory effect occurred following desialylation and desulfation. 3. The channel in the presence of epidermal growth factor (EGF) and ATP responded by an increase in tyrosine phosphorylation of 55 and 170 kDa proteins, and the phosphorylated channels showed a 46% increase in 45Ca2+ uptake. The phosphorylation and the calcium uptake were susceptible to inhibition by a specific tyrosine kinase inhibitor, genistein. 4. The binding of EGF to calcium channel receptor protein was inhibited by the low and high molecular weight acidic mucins, causing 41.2 and 36.1% reduction, respectively. This reduction in binding was dependent upon the presence of sulfate ester and sialic acid groups, as evidenced by the loss of the glycoproteins' inhibitory capacity following removal of these groups. 5. The results for the first time demonstrate that salivary mucins actively participate in the modulation of the EGF-controlled buccal mucosal calcium channel activity expression, a process of importance to the preservation of oral tissue integrity.

Calcium↗
PubMed1993

Modulation of gastric mucosal calcium channel activity by mucus glycoprotein.

1. The effect of gastric mucus glycoprotein on the activity of calcium channel isolated from gastric epithelial cell membrane was investigated. The 45Ca2+ uptake into the vesicle-reconstituted channels, while only moderately (14%) affected by the intact mucus glycoprotein, was found significantly inhibited (59%) by the acidic glycoprotein fraction. This effect was associated with the sialic acid and sulfate ester groups of the glycoprotein, as their removal caused a loss in the inhibition. 2. The channel complex in the presence of epidermal growth factor (EGF) and ATP responded by an increase in protein tyrosine phosphorylation of 55 and 170 kDa proteins, and the vesicles containing the phosphorylated channels showed a 50% increase in 45Ca2+ uptake. The phosphorylation and the calcium uptake were susceptible to inhibition by a specific tyrosine kinase inhibitor, genistein. 3. The channel protein phosphorylation was inhibited by the acidic mucus glycoprotein, which also interfered with the binding of EGF to the channel protein. The inhibitory effect was dependent upon the presence of sulfate ester and sialic acid groups, as evidenced by the loss of the glycoprotein inhibitory capacity following their removal. 4. The results suggest that the acidic gastric mucus glycoproteins, by modulating the EGF-controlled calcium channel phosphorylation, play a major role in gastric mucosal calcium homeostasis.

Adenosine Triphosphate↗
PubMed1993

Inhibition of Helicobacter pylori glycosulfatase activity towards human gastric sulfomucin by a gastroprotective agent, sulglycotide.

1. A glycosulfatase activity towards human gastric sulfomucin was identified in the extracellular material elaborated by Helicobacter pylori, a pathogen implicated in the etiology of gastric disease. 2. The purified enzyme displayed an apparent molecular weight of 30 kDa, and exhibited maximum activity at pH 5.7 in the presence of 0.3% Triton X-100 and 100 mM CaCl2. 3. The H. pylori glycosulfatase activity towards human gastric sulfomucin was inhibited by a gastroprotective agent, sulglycotide. The inhibitory effect was proportional to the concentration of sulglycotide up to 20 micrograms/ml, at which a 98% decrease in mucin desulfation occurred. However, the drug lost the inhibitory effect following its chemical desulfation. 4. The results demonstrate that sulglycotide is a potent inhibitor of H. pylori glycosulfatase and, hence, may be of value in the treatment of gastric disease associated with this bacterial infection.

Anti-Ulcer Agents↗
PubMed1993

Modulation of buccal mucosal calcium channel activity by salivary mucins.

The effect salivary mucus glycoproteins on the activity of calcium channel isolated from buccal mucosal cell membranes was investigated. The channel complex following reconstitution into phospholipid vesicles exhibited an active 45Ca2+ uptake and responded to calcium channel activator, BAY K8644, and the antagonist, PN200-110. The uptake of 45Ca2+, while only moderately (15%) affected by the intact mucus glycoprotein was significantly inhibited (60-64%) by the acidic mucus glycoprotein fractions. This effect was associated with the sialic acid and sulfate ester groups of the carbohydrate chains. The channel complex in the presence of epidermal growth factor (EGF) and ATP responded by an increase in protein tyrosine phosphorylation of 55 and 170kDa proteins, and the vesicles containing the phosphorylated channels showed a 46% increase in 45Ca2+ uptake. The phosphorylation and the calcium uptake were susceptible to inhibition by a specific tyrosine kinase inhibitor, genistein. The binding of EGF to buccal mucosal calcium channel receptor protein was also inhibited (36-41%) by acidic mucus glycoprotein. The reduction in binding was dependent upon the presence of sulfate ester and sialic acid groups, as evidenced by the loss of the glycoprotein inhibitory capacity following removal of these groups. The results for the first time demonstrate that salivary mucins actively participate in the modulation of the buccal mucosal calcium channel activity, a process of importance to the preservation of soft oral integrity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗