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J Bilski

Publications and source records attributed to J Bilski.

At least 37 records · Page 2Linked to original sources
PubMed1989

Effects of growth hormone releasing factor on pancreatic secretion in vivo and in vitro.

Growth hormone releasing factor (GRF), a 44-residue peptide originally isolated from human pancreatic tumors, shows structural similarities to the members of the secretin-vasoactive intestinal peptide (VIP) peptides. This study was designed to determine the effects of human GRF (hGRF-(1-44] on pancreatic secretion in vivo in conscious dogs and in vitro in dispersed rat pancreatic acini. GRF given i.v. in graded doses in dogs caused a small but significant stimulation of pancreatic HCO3- and protein outputs and potentiated secretin- and cholecystokinin (CCK)-induced pancreatic HCO3- but not protein secretion. When given together with somatostatin, GRF failed to reverse the inhibitory action of this peptide on HCO3- and protein responses to secretin plus CCK in dogs. Studies in vitro dispersed rat pancreatic acini showed that GRF added to the incubation medium of these acini caused an increase in basal amylase release and shifted to the left the amylase dose-response curve to caerulein and urecholine but failed to affect the amylase response to VIP. This study indicates that GRF in vivo stimulates basal and augments secretin- or CCK-induced pancreatic HCO3- secretion and that this is probably due to direct stimulatory action of the peptide on pancreatic secretory cells.

Amylases↗
PubMed1989

Colloidal bismuth subcitrate (De-Nol) inhibits degradation of gastric mucus by Campylobacter pylori protease.

There is increased awareness that infection with Campylobacter pylori could be a major factor in the pathogenesis of gastric disease. Here, we present evidence that the extracellular protease elaborated by this bacteria, which causes degradation of gastric mucus, is inhibited by an antiulcer agent, colloidal bismuth subcitrate (CBS; De-Nol). The study was conducted with C. pylori cultured from antral mucosal biopsy specimens of patients undergoing gastroscopy. The grown colonies of bacteria were washed with saline, filtered through sterilization filter, dialyzed, and lyophilized. The powder was used as the enzyme source for proteolytic activity assay employing pig gastric mucus as substrate. Optimum enzymatic activity was obtained at 37 degrees C and at pH 7.0. The apparent Km of C. pylori protease with gastric mucus was 0.71 g/L. Analyses of the degradation products indicated that the protease caused extensive proteolysis of mucus glycoprotein polymer. Introduction of CBS to the incubation mixtures led to a reduction of the rate of mucus degradation. The rate of proteolysis inhibition was proportional to CBS concentration up to 1 X 10(-1) g/L, at which point a 37% reduction in mucus proteolysis was obtained. The Km value for proteolytic degradation of mucus by C. pylori protease in the presence of CBS was 1.25 g/L. The results suggest that CBS is capable of counter-acting the proteolysis of the protective gastric mucus layer by C. pylori.

Animals↗
PubMed1988

Sulfation in vitro of mucus glycoprotein by submandibular salivary gland: effects of prostaglandin and acetylsalicylic acid.

Enzymatic sulfation of mucus glycoprotein by rat submandibular salivary gland and the effect of prostaglandin and acetylsalicylic acid on this process were investigated in vitro. The sulfotransferase enzyme which catalyzes the transfer of sulfate ester group from 3'-phosphoadenosine-5'-phosphosulfate to submandibular gland mucus glycoprotein has been located in the detergent extracts of Golgi-rich membrane fraction of the gland. Optimum enzyme activity was obtained at pH 6.8 with 0.5% Triton X-100, 25 mM NaF and 4 mM MgCl2, using the desulfated glycoprotein. The enzyme was also capable of sulfation of the intact mucus glycoprotein, but the acceptor capacity of such glycoprotein was 68% lower. The apparent Km of the submandibular gland sulfotransferase for salivary mucus glycoprotein was 11.1 microM. The 35S-labeled glycoprotein product of the enzyme reaction gave in CsCl density gradient a 35S-labeled peak which coincided with that of the glycoprotein. This glycoprotein upon reductive beta-elimination yielded several acidic 35S-labeled oligosaccharide alditols which accounted for 75% of the 35S-labeled glycoprotein label. Based on the analytical data, the two most abundant oligosaccharides were identified as sulfated tri- and pentasaccharides. The submandibular gland sulfotransferase activity was stimulated by 16,16-dimethyl prostaglandin E2 and inhibited by acetylsalicylic acid. The rate of enhancement of the glycoprotein sulfation was proportional to the concentration of prostaglandin up to 2.10(-5) M, at which point a 31% increase in sulfation was attained. The inhibition of the glycoprotein sulfation by acetylsalicylic acid was proportional to the drug concentration up to 2.5.10(-4) M at which concentration a 48% reduction in the sulfotransferase activity occurred. The apparent Ki value for sulfation of salivary mucus glycoprotein in presence of acetylsalicylic acid was 58.9 microM. The results suggest that prostaglandins may play a role in salivary mucin sulfation and that this process is sensitive to such nonsteroidal anti-inflammatory agents as acetylsalicylic acid.

16,16-Dimethylprostaglandin E2↗
PubMed1988

Role of salivary epidermal growth factor in the maintenance of physicochemical characteristics of oral and gastric mucosal mucus coat.

The involvement of salivary epidermal growth factor (EGF) in the maintenance of oral and gastric mucosal mucus coat dimension and chemical characteristics was investigated using sialoadenectomized rats. Examination of the oral and gastric mucosal surface by phase contrast microscopy and Alcian blue uptake revealed that deprivation of salivary EGF caused a 31-36% reduction in mucus coat thickness and a 38-43% reduction in adherent mucin content. Chemical analyses indicated that the mucus coat of sialoadenectomized group exhibited a 21-28% increase in protein and a 67% decrease in covalently bound fatty acids, a 30% decrease in carbohydrates, and a 32-37% decrease in lipids. Sialoadenectomy also evoked changes in the chemical composition of mucus glycoprotein component of oral and gastric mucus coat reflected in the lower content of sulfate (25-26%), associated lipids (24-25%), and covalently bound fatty acids (67-75%). Intragastric supplementation of EGF had no effect on the physicochemical changes caused by sialoadenectomy in the oral mucosal mucus coat, while nearly complete restoration to normal characteristics occurred in the gastric mucosal mucus coat. The results suggest that salivary EGF is essential for the maintenance of mucus coat dimension and quality needed in the protection of alimentary tract epithelium.

Animals↗
PubMed1988

Effects of peptide YY on dog and rat pancreatic secretion in vivo and in vitro.

The action of peptide YY (PYY) on exocrine pancreatic secretion in dogs and rats was compared in in vivo and in vitro studies. PYY infused i.v. in the physiological dose range (125-1000 pmol/kg.h) reduced in a dose-dependent manner the pancreatic protein response to caerulein and suppressed basal and meat feeding or duodenal oleate-induced pancreatic secretion in conscious dogs. Both meat feeding and duodenal oleate caused significant elevation of plasma PYY levels and these showed several-fold increase during infusion of exogenous PYY (500 pmol/kg.h) inducing significant inhibition of the postprandial or oleate-stimulated pancreatic secretion. PYY in a dose range of 2.5-40 nmol/kg.h also inhibited the response to caerulein in conscious rats but failed to prevent the increment in the postprandial protein secretion in this species. PYY added in various concentrations (10(-11)-10(-6) M) to the incubation medium of the isolated dog and rat pancreatic acini failed to affect basal or caerulein- and urecholine-stimulated amylase release. This study shows that PYY is an effective inhibitor of the pancreatic secretion in vivo but not in vitro suggesting that the inhibition is mediated by an indirect mechanism.

Amylases↗
PubMed1988

Adrenergic pathway in the inhibition of pancreatic secretion by peptide YY in dogs.

Peptide YY (PYY) is released by perfusion of an ileocolonic segment with oleate and inhibits exocrine pancreatic secretion. This study was designed to determine the role of the adrenergic pathway in the PYY-induced inhibition of pancreatic secretion. After intravenous administration of PYY, there was a dose-dependent inhibition of pancreatic HCO3 and protein responses to secretin, cholecystokinin, and feeding in conscious dogs and a reduction in pancreatic blood flow in anesthetized animals. These inhibitory effects of PYY on pancreatic secretion and blood flow were abolished in the presence of combined phentolamine and propranolol. Ileal perfusion with oleate caused a rise in plasma PYY levels similar to that observed after intravenous infusion of exogenous PYY. Combined alpha- and beta-adrenergic blockade also antagonized the effects of ileal perfusion with oleate on hormonal and postprandial pancreatic secretion. We conclude that exogenous PYY or endogenous PYY released by ileal oleate inhibits pancreatic secretory responses to exogenous secretin, cholecystokinin, or a meal and causes pancreatic vasoconstriction. Both these effects are mediated, at least in part, by the adrenergic pathway.

Animals↗
PubMed1988

Protection against alcohol-induced gastric mucosal injury by geranylgeranylacetone: effect of indomethacin.

The mechanism of gastric mucosal protection by an antiulcer agent, geranylgeranylacetone (GGA), against ethanol-induced injury was investigated. The experiments were conducted with groups of rats with and without intraperitoneal indomethacin pretreatment. Animals received intragastrically either a dose of GGA (200 mg/kg) or a vehicle, followed 30 min later by 1 ml of absolute ethanol. The rats were sacrificed after 30 min and the gastric mucosa was subjected to macroscopic and histologic assessment and the measurements of adherent mucus, its dimension and chemical composition. In the absence of GGA, ethanol produced advanced macroscopic necrosis (greater than 38%) and the extensive necrotic lesions were visible upon histologic examination. Pretreatment with GGA significantly reduced (p less than 0.001) the extent and depth of mucosal necrotic lesions caused by ethanol, and this protection was not thwarted by indomethacin. Evaluation of the adherent mucus and its dimension by Alcian blue uptake and inverted microscope technique revealed that GGA was also capable of preventing the untoward effect of indomethacin on the adherent gastric mucus gel and its thickness. Results of chemical analyses established that in the absence of GGA indomethacin caused an increase in mucus protein (15%) and a decrease in its covalently bound fatty acids (67%) and lipids (36%). The decrease in lipids was particularly reflected in the content of phospholipids. Indomethacin, however, had no apparent effect on the composition of gastric mucus elaborated in the presence of GGA. The results suggest that gastric mucosal protective action of GGA is not mediated by endogenous prostaglandins but rather appears to involve the metabolism of mucosal lipids.

Animals↗
PubMed1988

Comparison of somatostatin and its highly potent hexa- and octapeptide analogs on exocrine and endocrine pancreatic secretion.

The effects on pancreatic responses of highly potent cyclic hexapeptide (cyclo (N-Me-Ala-Phe-D-Trp-Lys-Thr-Phe)) (Veber analog) and octapeptide analogs of somatostatin such as D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol (SMS 201-995), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) have been compared with somatostatin tetradecapeptide (SS-14) and atropine. The parameters evaluated were pancreatic responses to secretin and meat feeding in conscious dogs with chronic pancreatic fistula and amylase release from the dispersed pancreatic acini. The analogs were administered intravenously or intraduodenally. The cyclic hexapeptide and octapeptide analogs, given iv in graded doses against a constant background stimulation with secretin, produced similar and dose-dependent inhibition of pancreatic HCO3- and protein secretion. Analogs RC-121, RC-160, and the Veber analog were about two to four times more active than SS-14 in suppressing HCO3- secretion and equipotent in reducing protein secretion, but SMS 201-995 was only about half as potent as somatostatin in inhibiting HCO3-. RC-160 was effective in inhibiting secretin-induced protein secretion at lower doses than other analogs. In tests with feeding, SMS 201-995, the Veber analog, RC-121, and RC-160 were more potent inhibitors of exocrine pancreatic secretion of HCO3- and protein and exhibited more prolonged inhibitory effects than SS-14. The Veber analog, RC-121, and RC-160 were also more effective after intraduodenal administration. Atropine also caused significant inhibition of both HCO3- and protein responses to secretin and meal feeding. All four analogs decreased the postprandial insulin and pancreatic polypeptide release to a similar degree as SS-14. Neither SS-14 nor the analogs tested significantly affected basal or caerulein-, gastrin-, secretin-, or bethanechol-stimulated amylase release from the dispersed canine pancreatic acini. Atropine reduced amylase release induced by bethanechol, but not that stimulated by caerulein, gastrin, or secretin. This indicated that the analogs, as somatostatin, are ineffective as secretory inhibitors in vitro. We conclude that cyclic hexapeptide and octapeptide analogs are more potent and longer acting inhibitors of pancreatic secretion than somatostatin-14 in vivo.

Amylases↗
PubMed1987

Enhancement of the lipid content and physical properties of gastric mucus by geranylgeranylacetone.

The effects of intragastric administration of geranylgeranylacetone (GGA) on the content, composition and physical properties of the mucus component of the gastric mucosal barrier were investigated. One group of rats received twice daily for 3 consecutive days a dose of 100 mg/kg body weight of GGA, while the control group was subjected to daily doses of the vehicle. Sixteen hours following the last dose, the animals were killed, and their stomach was cut open and subjected to measurements of the adherent mucus gel content, analysis of its lipids and molecular forms of elaborated mucin, and evaluation of the viscosity and H+ retardation capacity. The results revealed that GGA elicited a 62% increase in the adherent mucus gel and caused a marked decrease in the proportion of the lower molecular weight mucin. Furthermore, the mucus of the GGA group exhibited a 67% higher content of covalently bound fatty acids and contained 46% more total lipids which were greatly (143%) enriched in phospholipids. The physical measurements demonstrated that mucus elaborated in the presence of GGA also exhibited 2.3 times higher viscosity and had a 32% greater ability to retard the diffusion of H+ than the mucus of the control group. The results suggest that GGA exerts a profound effect on the lipid content and the properties of gastric mucus associated with the maintenance of the mucosal integrity.

Animals↗
PubMed1987

Campylobacter pyloridis degrades mucin and undermines gastric mucosal integrity.

The role of Campylobacter pyloridis, a spiral bacteria associated with gastritis and peptic ulcers in weakening the mucus component of gastric mucosal barrier was investigated. The colonies of bacteria, cultured from antral mucosal biopsies of patients undergoing gastroscopy, were washed with saline, passed through sterilization filter and the filtrate was examined for protease and glycosylhydrolase activities. The obtained results revealed that the filtrate exhibited a strong proteolytic activity not only towards the typical protein substrates such as albumin but also towards gastric mucin. Optimum enzymatic activity for degradation of mucin was attained at pH 7.0 and the protease activity was found in a low m.w. (less than 50K) protein fraction. The filtrate showed little glycosylhydrolase activity and did not cause the hydrolysis of mucin carbohydrates. The data suggest that C pyloridis infection weakens the gastric mucosal defense by causing proteolytic degradation of mucin component of the protective mucus layer.

Campylobacter↗
PubMed1987

Role of secretin and CCK in the stimulation of pancreatic secretion in conscious dogs. Effects of atropine and somatostatin.

The role of gut hormones, such as secretin and CCK, in the stimulation of pancreatic secretion by duodenal HCl or oleate and by meat feeding has been studied in conscious dogs before and after pretreatment with atropine and somatostatin. Plasma hormones were measured by specific and sensitive radioimmunoassays. Duodenal perfusion with HCl and oleate stimulated dose-dependently pancreatic HCO3 and protein secretion and raised plasma levels of secretin and CCK, respectively. Atropine reduced significantly both HCO3 and protein secretion but did not affect plasma secretin and CCK levels in these studies. Both exocrine pancreatic secretion and plasma secretin and CCK levels were suppressed by somatostatin. Meat feeding caused a marked pancreatic HCO3 and protein secretion accompanied by a significant increase in plasma secretin and CCK which seem to play an important role in the postprandial pancreatic stimulation. Both atropine and somatostatin reduced the pancreatic secretion induced by exogenous hormones but only somatostatin, but not atropine, significantly decreased plasma secretin and CCK responses to intestinal stimulants. We conclude that both atropine and somatostatin reduce the pancreatic responses to duodenal HCl or oleate or to meat feeding but only somatostatin is capable of suppressing the release of secretin and CCK.

Animals↗
PubMed1987

Intestinal release of mucin in response to HCl and taurocholate: effect of indomethacin.

1. Alkaline secretion and mucin output were analyzed along the gastrointestinal tract of a dog in response to luminal application of HCl and taurocholate with and without pretreatment with indomethacin. 2. Mucins derived from the different areas displayed similar contents of protein and carbohydrate but differed with respect to associated and covalently bound lipids. 3. Application of HCl or taurocholate in all the regions caused an increase in the output of mucins and HCO3-. However, mucins elaborated in response to HCl exhibited higher total lipid content and were richer in phospholipids. 4. Pretreatment with indomethacin prior to HCl application led to a reduction in HCO3- and caused a decrease in mucin phospholipid content, but had no effect on HCO3- secretion and the lipid content of mucins elaborated in response to taurocholate. 5. The results indicate that mucins elaborated along the gastrointestinal tract differ with respect to lipids, and that their output in response to HCl is mediated by prostaglandins.

Animals↗
PubMed1987

Effects of leukotrienes on gastric acid and alkaline secretions.

This study was designed to determine the influence of leukotriene C4 on gastric acid and alkaline secretion. Leukotriene C4 was found to be a potent inhibitor of gastric acid secretion induced in vagally innervated and denervated portions of the stomach of conscious dogs by a variety of stimulants such as histamine, pentagastrin, and meat feeding. Leukotriene C4 was also an effective inhibitor of acid formation in the isolated gastric glands stimulated by histamine or dibutyryl cyclic adenosine monophosphate without or with addition of indomethacin, indicating that this compound acts directly on the parietal cells without mediation of endogenous prostaglandins. Leukotriene C4 was also an effective stimulant of gastric alkaline secretion. However, this effect was probably mediated by an increase in the generation of endogenous prostaglandin, as it was accompanied by an increase in the luminal release of prostaglandin E2 and indomethacin prevented both the stimulation of alkaline secretion and luminal prostaglandin E2 release by leukotriene C4.

Animals↗
PubMed1987

De-Nol stimulates gastric and duodenal alkaline secretion through prostaglandin dependent mechanism.

This study was designed to determine the effects of colloidal bismuth subcitrate De-Nol on gastric HCO3- secretion in 24 healthy subjects and on gastric and duodenal HCO3- secretion in dogs with gastric and duodenal fistulae. Alkaline secretion was measured after pretreatment with ranitidine to abolish the H+ secretion using a constant perfusion aspiration system and back titration of the perfusates to the original pH 6.0. Luminal release of PGE2 was also measured in the gastric and duodenal perfusates. Addition of De-Nol in gradually increasing concentrations resulted in step wise increments in gastric HCO3- secretion in man and in dogs reaching, respectively, about 80% and 55% of the maximal HCO3- response to 16, 16dimethyl-PGE2 (dmPGE2). The duodenal HCO3- response to De-Nol in dogs reached 72% of the dmPGE2 maximum. These effects were accompanied by a significant increase in luminal release of PGE2. Pretreatment with atropine reduced basal and in part De-Nol induced alkaline secretion, whereas pirenzepine did not affect this secretion in man and dogs. Aspirin (in man) and indomethacin (in dogs) reduced the release of PGE2 by about 80% and suppressed almost completely the gastric and duodenal HCO3- response to De-Nol in these species. This study provides evidence that De-Nol stimulates gastroduodenal alkaline secretion through a prostaglandin dependent mechanism.

Adult↗
PubMed1987

Cephalic phase of gastroduodenal alkaline secretion.

Alkaline secretion measured under basal conditions in the intact stomach of conscious dogs averaged 47 mumol/30 min and was about twice lower than that recorded in the proximal (approximately 7 cm long) portion of the duodenum. Vagal excitation elicited by sham feeding and insulin resulted in a marked stimulation of alkaline secretion both from the stomach and the duodenum. Atropine significantly reduced gastric and duodenal alkaline secretion under basal state. It abolished gastric and diminished duodenal alkaline response to sham feeding and insulin hypoglycemia, while propranolol was without significant influence. Indomethacin reduced by approximately 75% basal duodenal alkaline secretion but did not prevent the increment in alkaline response to vagal stimulation. We postulate the existence of the cephalic phase of gastroduodenal alkaline secretion, which seems to be cholinergically dependent in the stomach and partly of noncholinergic and nonadrenergic character but prostaglandin dependent in the duodenum.

Animals↗
PubMed1987

Effect of solon on gastric mucus viscosity, permeability to hydrogen ion, and susceptibility to pepsin.

The effect of a new antiulcer drug, solon (sofalcone), on gastric mucus viscosity, permeability to hydrogen ion and degradation by pepsin was investigated using an in vitro system. Preincubation of the isolated gastric mucus with solon produced a marked enhancement in mucus viscosity. This enhancement was concentration dependent and at 2.2 X 10(-1) M solon reached a value of 230%. Permeability measurements showed that 2.2 X 10(-2) M solon increased the retardation ability of mucus to hydrogen ion by 32%, while 43% increase was obtained with 2.2 X 10(-1) M solon. The drug had no effect on the viscosity and hydrogen ion retardation capacity of albumin. The results of peptic activity assay indicated that solon had an inhibitory effect on the rate of mucus and albumin proteolysis. The rate of inhibition of peptic activity was proportional to the solon concentration up to 1.0 X 10(-5) M, at which concentration the proteolysis of mucus was inhibited by 60% and that of albumin by 45%. The results obtained here under in vitro conditions suggest that solon, by inhibiting peptic erosion of the mucus layer, increasing its viscosity and enhancing the ability to impede the hydrogen ion penetration, strengthens the gastric mucosal integrity and thus could aid in ulcer healing.

Animals↗
PubMed1986

Physiological role and localization of cholecystokinin release in dogs.

In dogs with pancreatic fistulas, meat feeding and intestinal perfusion with a sodium oleate or amino acid mixture increased pancreatic protein secretion to approximately 110, 100, and 50%, respectively, of the response to cholecystokinin (CCK) at a dose of 85 pmol X kg-1 X h-1. Plasma CCK response increased in these studies to approximately 100, 180, and 40%, respectively, of the value obtained with exogenous CCK, suggesting that, in addition to CCK, other neurohormonal factors contribute to pancreatic enzyme secretion in response to endogenous stimulants. Feeding and duodenal oleate or amino acids also stimulate the release of pancreatic polypeptide (PP), which may be involved in the control of pancreatic secretion in response to endogenous stimulants, including CCK. Perfusion of the intact intestine with graded amounts of oleate (0.5-16 mmol/h) produced dose-dependent increments in plasma CCK and pancreatic protein similar to those obtained with intravenous infusion of graded doses of CCK (0.85-255 pmol X kg-1 X h-1). Oleate perfusion of isolated Thiry loops (30 cm long) made of duodenojejunal (D-J) and ileal (I) segments also stimulated protein secretion but elevated plasma CCK only after perfusion of the D-J but not of the I loop. We conclude that 1) the endogenous CCK released by various luminal stimulants drives the pancreatic protein secretion; 2) the release of CCK is confined to the foregut; and 3) PP concomitantly released by various intestinal stimulants may contribute to the control of pancreatic secretion induced by endogenous CCK.

Animals↗