Biomedical subjects

E Piotrowski

Publications and source records attributed to E Piotrowski.

At least 19 recordsLinked to original sources

PubMed2001

Early diagnosis of retroperitoneal necrotizing fasciitis.

OBJECTIVE: To report survival of retroperitoneal necrotizing fasciitis in an inmunocompromised patient and to demonstrate early clinical signs that may help in the prompt diagnosis and treatment of this severe infection. DESIGN: Case report and literature review. SETTING: An adult, 18-bed intensive care unit within a university hospital. PATIENT: A 38-yr-old man who had undergone an uncomplicated closed hemorrhoidectomy was readmitted to the hospital on postoperative day 5 for erythema around the hemorrhoidectomy and a dirty brown discharge from the wound. INTERVENTIONS: Early diagnosis of retroperitoneal necrotizing fasciitis, wide and repeated debridement, broad-spectrum antibiotics, and eventual abdominal wall reconstruction. MEASUREMENTS AND MAIN RESULTS: This patient manifested periumbilical and bilateral flank erythema, reminiscent of the pattern of ecchymosis seen in cases of retroperitoneal hemorrhage. The findings demonstrate a variation of Cullen's and Grey Turner's sign, most often found in patients with hemorrhagic pancreatitis. An abdominal radiograph revealed a ground glass appearance with radiolucency outlining the bladder, consistent with retroperitoneal air. The chest radiograph showed mediastinal air extending into the neck. Sharp debridement of the retroperitoneal fat, the right anterior rectus sheath, and the right anterior thigh fascia was required to gain control of the infection. Operative cultures grew a mixed flora with Eschericha coli, beta-hemolytic streptococcus, and Bacteroides fragilis predominating. The hospital course was complicated by hemodynamic instability, renal failure, pneumonia, and a pelvic abscess. The patient ultimately survived and underwent abdominal wall reconstruction with mesh. CONCLUSION: Retroperitoneal necrotizing fasciitis is an uncommon soft tissue infection that is often fatal. Early diagnosis in this case was facilitated by the unique clinical findings of a modified Cullen's and Grey Turner's sign. A review of the limited available literature suggests that survival of retroperitoneal fasciitis is possible with prompt debridement and antibiotic therapy.

Adult↗

PubMed2000

Impact of ethanol on innate protection of gastric mucosal epithelial surfaces and the risk of injury.

Earlier investigations on the effect of ethanol on synthesis and posttranlational glycosylation of gastric mucus glycoprotein (mucin) revealed quantitative changes in the apoprotein assembly, glycosylation, and mucin retention on the mucosal surface (Slomiany et al.., Alcoholism: Clin. Exp. Res. 21, 417-423, 1998). To assess whether metabolic consequences of ethanol ingestion, documented in the in vitro system are also occurring in vivo the rats were subjected to 8 weeks of ethanol containing liquid diet. The retention of mucin on the surface of gastric mucosa was quantitated by measuring the binding of gastric mucin to Mucin Binding Protein (MBP) of gastric mucosa. The results were compared with those obtained with the rats subjected to pair-feeding the isocaloric-control diet. Before alcohol administration, and in two weeks' intervals thereafter, the gastric contents from the animals was collected and mucin purified. After 8 weeks of the respective diet, the animals were sacrificed and their gastric mucosa used for MBP preparation. The binding of mucin to MBP before ethanol, and after 2, 4, 6, and 8 weeks of ethanol diet was quantitated with Enzyme Linked Lectin Assay (ELLA). The study with standard mucin revealed that binding of mucin to MBP differs substantially between individual animals. The same variability in binding was observed with the individual mucin preparations collected at the onset of the experiment. However, with the progression of ethanol feeding, the mucin samples besides displaying the variable and animal-specific binding to MBP at the initiation of the experiment, also showed a dramatic decrease in binding. In five animals, after two weeks of ethanol diet, mucin binding to MBP decreased by 50%; in two animals, the drastic decrease in binding was observed in mucin collected after four weeks of alcohol feeding; and in one animal a 20% decrease in binding persisted for six weeks, and then decreased to 50% in the last collection. Also, in two animals, the mucin collected after 8 weeks of ethanol feeding retained only 6-9% of the initial binding capacity. In contrast, in pair-fed controls, the mucin binding to MBP remained the same or increased up to 20%. Results of the studies, performed on mucin of the individual animals and matching preparations of MBP, showed that each animal expresses different degree of mucin binding. Moreover, in chronic ethanol ingestion, the individual variations are accompanied by a decrease in mucin binding to MBP. Since the observed decrease in binding occurred in samples containing the same preparation of MBP, the component affected by alcohol resides on mucin. Thus, considering the in vitro impact of ethanol on generation of carbohydrate chains in Golgi, and the finding on mucin oligosaccharides-dependent mucin-MBP complex formation, we conclude that ethanol impairs the synthesis of mucin oligosaccharide structures required for binding with MBP, and the retention on gastric mucosal surfaces.

Alcohol Drinking↗

PubMed1999

Chronic ethanol-initiated apoptosis in hepatocytes is induced by changes in membrane biogenesis and intracellular transport.

The outcome of chronic ethanol consumption recorded in liver by in situ staining of the genomic DNA in fragmented nuclei indicates the course of cellular events that has been coined as apoptosis or programmed cell death. Hence, we designed the study to determine which ethanol-induced modification of the cellular make-up is responsible for the hastening the cell damage. The in vitro assays were performed with cellular organelles and cytosol prepared from hepatocytes derived from rats subjected to 9 weeks of chronic alcohol consumption. The results were compared with the pair-fed controls receiving isocaloric liquid diet. In the initial phase of the studies, we established that the process of apoptosis was not triggered by the aberrant activity of neutral or acidic sphingomyelinase. The hepatocytes derived from alcohol and control diets manifested equal enzymatic activity. The de novo synthesis of sphingoid bases and ceramides in the alcohol-derived sample of endoplasmic reticulum was reduced, but the in situ apoptosis was up to 36-fold higher than in the control. Also, the isolated hepatocytes contained a 2- to 4-fold higher amount of nucleosomal fragments in the cytosolic extracts. The endosomes from liver hepatocytes of ethanol-consuming rats, in the presence of the cytosol and mitochondria from pair-fed controls, disclosed 2 to 3 times higher apoptotic potential than sample consisting of ethanol-derived fractions only, and 3 to 5 times higher than the control-derived fractions. The substantial increase in apoptosis, as recorded in the amount of DNA fragments released to the cytosol from the fresh nuclei, was also recorded when the microsomal membranes of endoplasmic reticulum and Golgi were incubated in the conditions with preserved intracellular transport. The maximal 20-fold increase of apoptotic activity was recorded in the incubation mixtures of ethanol-derived endoplasmic reticulum-Golgi membranes with control-derived cytosol in the presence of the ATP generating system. Results infer that the intracellular transport vesicles, generated from ethanol-modified membranes in the presence of the substrates that are available in the cytosol of the control hepatocytes, activate the apoptotic activity in the in vitro system. This interpretation is supported by the results of analysis of the clathrin-coated transport vesicles that, in contrast to nonclathrin transport vesicles, contain a sizable accumulation of ceramides that are known to induce apoptosis.

Animals↗

PubMed1998

Induction of buccal mucosal apoptosis with chronic alcohol ingestion.

In this study we investigated buccal mucosal cells apoptosis and the expression of regulatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-4(IL-4) with chronic ethanol ingestion. The buccal mucosa of rats maintained for 23 days on alcohol-containing and control liquid diet was assessed for IL-4 and TNF-alpha content, and the extent of epithelial cells apoptosis. While the expression of TNF-alpha in alcohol diet group showed a significant increase (1.9-fold) over that of the controls, less apparent differences between the two groups were observed in the content of IL-4 (141.8 +/- 28.2 vs. 119.8 +/- 7.3 pg/mg protein). The DNA fragmentation assays revealed that alcohol diet group also exhibited a 3.5-fold enhancement in buccal mucosal cells apoptosis. Moreover, the apoptotic index showed positive correlation (r = 0.53) with the extent of induced changes in TNF-alpha. These results demonstrate that ethanol-induced buccal mucosal cells apoptosis is triggered by the enhancement in TNF-alpha expression.

Alcoholism↗

PubMed1998

Activation of apoptotic caspase-3 and nitric oxide synthase-2 in buccal mucosa with chronic alcohol ingestion.

Apoptosis, the process of programmed cell death, involves activation of caspase proteases cascade that remains under the regulatory control of nitric oxide. In this study, we investigated the activity of a key apoptotic protease, caspase-3, and the expression of nitric oxide synthase-2 (NOS-2) associated with buccal epithelial cells apoptosis induced by chronic ethanol diet. The assays revealed that a 7.9-fold enhancement in buccal epithelial cells apoptosis, observed in the alcohol diet group, was accompanied by a 37.6-fold increase in caspase-3 activity and a 10.1-fold increase in NOS-2. Furthermore, the expression of NOS-2 showed a positive correlation (r = 0.92) with the extent of changes induced in caspase-3 activity. These results implicate caspase-3 in the process of alcohol-induced epithelial cells apoptosis, and point towards participation of NOS-2 in the amplification of the cell death signaling cascade.

Alcoholism↗

PubMed1998

Effect of ethanol on intracellular vesicular transport from Golgi to the apical cell membrane: role of phosphatidylinositol 3-kinase and phospholipase A2 in Golgi transport vesicles association and fusion with the apical membrane.

The study of ethanol effects on intracellular transport and membrane biogenesis in rat hepatocytes revealed that, during synthesis of transport vesicles, the cytosolic phosphatidylinositol 3-kinase incorporated into the membrane of Golgi transport vesicles and a portion of the vesicular phosphatidylinositol was phosphorylated to phosphatidylinositol 3-phosphate. Association of the enzyme with Golgi transport vesicles and the transport to the apical portion of the cell membrane was not affected by 0 to 120 mM ethanol, but was dependent on the presence of the p85 subunit of the phosphatidylinositol 3-kinase. In the presence of ATP-enriched cytosol and calcium ions, association of Golgi transport vesicles with the apical membrane was followed by phospholipase A2-specific hydrolysis of phosphatidylinositol 3-phosphate and incorporation of the transport vesicle membrane into the apical membrane. Association of Golgi transport vesicles with apical membranes was not affected by preincubation of the cell membrane or Golgi transport vesicles with 0 to 120 mM ethanol, but was inhibited when the p85 phosphatidylinositol 3-kinase was incorporated into the membrane before incubation with Golgi transport vesicles. The fusion of Golgi transport vesicles with the apical membrane and generation of lysophosphatidylinositol 3-phosphate and arachidonate was inhibited with EGTA or after depletion of ATP from cytosol. Results of these studies provide evidence that phosphatidylinositol 3-kinase and phospholipase A2 activities are crucial for the final step of exocytotic transport. The process consists of two stages. First, the p85 subunit of phosphatidylinositol 3-kinase is involved in the specific association of the vesicle with membrane receptor, and that is followed by phospholipase A2-specific lysophospholipid generation, perturbation of the membranes, and fusion of the transport vesicle membrane with the apical membrane. Addition of ethanol to the in vitro transport system decreased production of Golgi transport vesicles, but had no effect on their association with apical membrane or fusion with the membrane.

Animals↗

PubMed1997

Gastric mucosal apoptosis induced by ethanol: effect of antiulcer agents.

In this study, we investigated gastric epithelial cells' apoptosis and tumor necrosis factor-alpha (TNF-alpha) expression with ethanol-induced mucosal injury, and the effect of antiulcer agents on this process. Rats received intragastric pretreatment with the agent or vehicle followed 1h later by ethanol, and after 30 min the gastric mucosa was assessed for TNF-alpha and apoptosis. In the absence of antiulcer agents, ethanol caused extensive mucosal lesions accompanied by a 9.5-fold enhancement in apoptosis and a 2.5-fold increase in TNF-alpha. Pretreatment with omeprazole evoked a 54% reduction in TNF-alpha, but had no effect on ethanol-induced mucosal damage or apoptosis, the sucralfate reduced the extent of mucosal damage by 95%, apoptosis by 39% and TNF-alpha by 52%, while ebrotidine not only prevented mucosal injury and rise in TNF-alpha, but also caused a 70% reduction in epithelial cells' apoptosis. The results demonstrate that ethanol-induced gastric epithelial cells apoptosis triggered by the enhancement in mucosal TNF-alpha is efficiently counteracted by ebrotidine.

Animals↗

PubMed1997

Induction of acute gastritis and epithelial apoptosis by Helicobacter pylori lipopolysaccharide.

BACKGROUND: The preservation of gastric mucosal homeostasis is a complex biologic process, controlled by a dynamic equilibrium of cell loss by apoptosis with that of cellular proliferation, and its abrogation is a prominent feature of Helicobacter pylori-associated gastritis. In this report, we show that H. pylori lipopolysaccharide induces histologic lesions typical of acute gastritis and that these changes are reflected in the increased epithelial cell apoptosis. METHODS: The experiments were conducted with groups of rats subjected to intragastric surface epithelial application of the lipopolysaccharide at 50 and 200 micrograms per animal. The histologic assessment of the mucosal tissue and quantification of apoptotic epithelial cells was performed 2 and 10 days after the lipopolysaccharide treatment. RESULTS: Histologic examination showed that H. pylori lipopolysaccharide at both doses within 2 days induced infiltration of lamina propria with lymphocytes and plasma cells, edema, hyperemia, and hemorrhage extending from the lamina propria to the surface of mucosa, and the effect persisted beyond the 10 days. The in situ DNA fragmentation assay showed that lipopolysaccharide caused a marked increase in epithelial cell apoptosis, with the numerous apoptotic cells present not only in the superficial epithelium but also deeper in the glands. The mean apoptotic index in the mucosa was 59% when assessed 2 days after the administration of the 50-microgram lipopolysaccharide dose and 71.9% after the 200-microgram dose, whereas in the sections assessed 10 days after the lipopolysaccharide treatment the apoptotic index averaged 46% for a 50-microgram dose and 76.8% for a 200-microgram dose. Moreover, the apoptotic index showed positive correlation (r = 0.71) with the grade of the induced inflammatory changes. CONCLUSIONS: Our findings demonstrate that H. pylori lipopolysaccharide can cause gastric mucosal responses typical of acute gastritis and identify the lipopolysaccharide as a virulence factor responsible for the induction of gastric epithelial cell apoptosis by H. pylori.

Animals↗

PubMed1995

Susceptibility of Helicobacter pylori to antimicrobial agents: effect of ebrotidine and ranitidine.

Convincing evidence now exists that infection with H. pylori is a primary factor in the pathogenesis of gastric disease, and new therapy regimens include a combination of H2 blockers with antimicrobial agents. In this study, was assessed the effect of ebrotidine and ranitidine on the in vitro anti-H. pylori activity of amoxicillin, erythromycin, tetracycline, and metronidazole. The assays of the antiulcer drugs alone gave MIC value of 150 mg/L for ebrotidine and 1600 mg/L for ranitidine. Inclusion of ebrotidine in the antimicrobial agent assays evoked at its optimal concentration of 75 mg/L a 28% enhancement in the MIC of metronidazole, 2.5-fold enhancement in the MIC of erythromycin, 2-fold in amoxicillin and 1.7-fold in tetracycline, while ranitidine caused noticeable changes in the MIC values of the tested antimicrobial agents only a the dose of 1600 mg/L. The results demonstrate that ebrotidine enhances anti-H. pylori activity of antimicrobial agents at doses well below that of ranitidine.

Anti-Bacterial Agents↗

PubMed1994

Intracellular processes associated with vesicular transport from endoplasmic reticulum to Golgi and exocytosis: ethanol-induced changes in membrane biogenesis.

Membrane biogenesis, expressed in endoplasmic reticulum (ER) by formation of transport vesicles, was studied in the liver of ethanol-fed and pair-fed rats. In ER of ethanol-fed animals, the endogenous synthesis of phosphatidylcholine (PC) and its contribution to ER transport vesicles were reduced by 50%, as compared to that in pair-fed controls. Reduction of PC synthesis and of its presence in ER-transport vesicles was also observed in pair-fed controls when the native cytosol was replaced with that from ethanol-fed animals. In contrast, preincubation of ER membranes from ethanol-fed animals with cytosol from controls led to the stimulation of PC synthesis in ER and its contribution to ER-transport vesicles. Analysis of water soluble metabolites of [methyl-14C]choline phosphate revealed the accumulation of CDP-choline precursor in samples derived from ethanol-fed rats. Concomitantly, the endogenous synthesis of phosphatidylinositol (PI) in the ER of ethanol-fed animals was stimulated up to 400-500%, but declined when the cytosol from ethanol-fed rats was replaced with that from the controls. The restoration of PC synthesis, the normalization of PI synthase activity, and, similar to control, the contribution of PC to ER-transport vesicles in ethanol-fed animals was achieved when ER membranes were preincubated with diglycerides or the cytosol was treated with ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA). Conversely, addition of CaCl2-EGTA buffer containing 3 microM free Ca2+ to control samples, led to a reduction in PC synthesis. The studies on the effect of free Ca2+ on PI synthase and phosphatidic acid (PA) phosphatase activity established that in the presence of 1-3 microM free Ca2+, PI synthase activity remained constant, whereas that of PA phosphatase was reduced by 40% at 1 microM Ca2+, and no activity was detected when free Ca2+ was adjusted to 3 microM. The results suggest that modified membrane biogenesis in the liver of ethanol-fed rats is connected to the elevated free Ca2+ in the cytosol, which appears to regulate phosphatase activity. Accumulation of CDP-choline, decreased activity of PA phosphatase, and increased contribution of PI lipids to ER-transport vesicle membrane suggest that in ethanol-fed animals diglycerides are depleted and PA is utilized in a CDP-diacylglycerol pathway, thus leading to the generation of a different group of phospholipids and consequently modified ER-transport vesicle membrane.

Alcohol Drinking↗

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

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↗

PubMed1992

Role of adrenergic and cholinergic mediators in salivary phospholipids secretion.

The influence of adrenergic and cholinergic mediators on phospholipid secretion in rat sublingual salivary gland cells maintained in the presence of [3H]choline was investigated. The secretion of [3H]choline-containing phospholipids over 30 min period averaged 1.93% of the total cellular labeled phospholipids in the absence of any mediator, and was enhanced by beta-adrenergic agonist, isoproterenol, to a greater extent than the cholinergic agonists, pilocarpine and carbachol. A 2.9-fold increase in phospholipid secretion occurred with isoproterenol, while pilocarpine and carbachol evoked only 1.3-fold increase. The effect of isoproterenol was inhibited by alprenolol and that of pilocarpine and carbachol by atropine. In contrast to pilocarpine and carbachol, the enhanced phospholipid secretion due to isoproterenol was accompanied by an increase in cAMP concentration. The secretion of phospholipids was also stimulated by dibutyryl-cAMP and the protein kinase C activator, phorbol myristate acetate, but not by 4 alpha-phorbol 12,13-didecanoate which does not activate protein kinase C. Furthermore, the effects of dibutyryl-cAMP and phorbol myristate acetate were additive. The phospholipids secreted in response to isoproterenol exhibited a 52% decrease in lysophosphatidylcholine, while those secreted in response to pilocarpine and carbachol showed a 21-23% lower content of phosphatidylcholine, and were enriched in lysophosphatidylcholine (2.6-2.8-fold) and sphingomyelin (1.5-1.6-fold). The results indicate that salivary phospholipid secretion remains mainly under beta-adrenergic regulation, while the phospholipid makeup of the secretion is under cholinergic control.

Adrenergic beta-Agonists↗

PubMed1992

Control of gastric mucus phospholipid content and composition by cholinergic and adrenergic mediators.

1. The secretion of choline-containing phospholipids by gastric mucosal cells in response to neural mediators was investigated using beta-adrenergic and cholinergic agents. 2. A 2.7-fold increase in phospholipid secretion occurred with isoproterenol, while pilocarpine evoked 1.4-fold increase and the effects were inhibited by the respective antagonists. 3. The phospholipid secretory responses were stimulated by dibutyryl-cAMP and phorbol myristate acetate (PMA), but not by 4 alpha-phorbol-12,13-didecanoate which does not activate protein kinase C. The effects of dibutyryl-cAMP and PMA were additive, the the PMA induced phospholipid secretion was inhibited by a protein kinase C inhibitor, tetracaine. 4. The phospholipids secreted in response to isoproterenol showed a 2.1-fold decrease in lysophosphatidylcholine, while those secreted in response to pilocarpine were enriched 2.3-fold in lysophosphatidylcholine, and 1.5-fold in sphingomyelin, and showed 23% lower content of phosphatidylcholine. 5. The results suggest that cholinergic and beta-adrenergic mediators participate in defining the gastric mucus phospholipid content and composition, and hence influence the mucosal protective capability.

Adrenergic beta-Agonists↗

PubMed1992

Adrenergic and cholinergic regulation of gastric mucus phospholipid secretion.

The influence of adrenergic and cholinergic agonists on phospholipid secretion in gastric mucosal cells maintained in the presence of [3H]choline was investigated. The secretion of [3H]choline phospholipids over a 30-min period averaged 1.98% of the total cellular labeled phospholipids in the absence of any mediator and was enhanced by the beta-adrenergic agonist isoproterenol to a greater extent than by the cholinergic agonist pilocarpine. A 2-fold increase in phospholipid secretion was achieved with isoproterenol, whereas pilocarpine produced a 1.3-fold increase. The stimulatory effect of isoproterenol was inhibited by alprenolol, and that of pilocarpine by atropine. The phospholipids secreted in response to isoproterenol showed a 30% decrease in lysophosphatidylcholine, whereas a 2.1-fold enrichment in this phospholipid occurred with pilocarpine. The results demonstrate the involvement of neural mediators in the regulation of phospholipid secretion in gastric mucus.

Alprenolol↗

PubMed1992

Control of salivary phospholipid content and composition.

The mediation of phospholipid secretion in rat sublingual salivary gland cells maintained in the presence of [3H]choline was investigated. The secretion of [3H]choline-containing phospholipids was enhanced by beta-adrenergic agonist, isoproterenol, to a greater extent than the cholinergic agonist carbachol. A 2.9-fold increase in phospholipid secretion occurred with isoproterenol, while carbachol evoked only about 1.3-fold increase. In contrast to carbachol, the enhanced phospholipid secretion due to isoproterenol was accompanied by an increase in cAMP concentration. The secretion of phospholipids was also stimulated by dibutyryl-cAMP and the protein kinase C activator, phorbol myristate acetate, but not by 4 alpha-phorbol 12, 13-didecanoate which does not activate protein kinase C. Furthermore, the effects of dibutyryl-cAMP and phorbol myristate acetate were additive. The phospholipids secreted in response to isoproterenol exhibited a 52% decrease in lysophosphatidylcholine, while those secreted in response to carbachol showed a 23% lower content of phosphatidylcholine, and were enriched in lysophosphatidylcholine (2.8-fold) and sphingomyelin (1.4-fold). The results suggest that salivary phospholipid secretion remains mainly under beta-adrenergic control, while the phospholipid makeup is under cholinergic regulation.

Animals↗

PubMed1991

Role of adrenergic and cholinergic mediators in gastric mucus phospholipid secretion.

The role of adrenergic and cholinergic mediators in phospholipid secretion by gastric mucosal cells maintained in the presence of [3H]choline was investigated. The secretion of [3H]choline phospholipids over 30 min period averaged 1.98% of the total cellular labeled phospholipids in the absence of any mediator, and was enhanced by beta-adrenergic agonist, isoproterenol, to a greater extent than the cholinergic agonist, pilocarpine. A 2-fold increase in phospholipid secretion was achieved with isoproterenol, while pilocarpine evoked 1.3-fold increase. The stimulatory effect of isoproterenol was inhibited by alprenolol and that of pilocarpine by atropine. The phospholipids secreted in response to isoproterenol exhibited a 30% decrease in lysophosphatidylcholine, while 2.1-fold enrichment in this phospholipid occurred with pilocarpine. The results, for the first time, demonstrate the involvement of neural mediators in the regulation of phospholipid secretion in gastric mucus.

Alprenolol↗