Wyniki wyszukiwania

1

Brain-gut axis in the modulation of pancreatic enzyme secretion

100%

Jaworek J., Nawrot-Porabka K., Leja-Szpak A., Konturek S. J.

Journal of Physiology and Pharmacology

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2010

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tom 61

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nr 5

2

Melatonin stimulates HSP27 phosphorylation in human pancreatic carcinoma cells [PANC-1]

88%

Leja-Szpak A., Jaworek J., Szklarczyk J., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology. Supplement

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2007

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tom 58

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nr 3

177-188

3

Leptin is able to stimulate pancreatic enzyme secretion via activation of duodeno-pancreatic reflex and CCK release

76%

Nawrot-Porabka K., Jaworek J., Leja-Szpak A., Palonek M., Szklarczyk J., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology. Supplement

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2004

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tom 55

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nr 2

47-57

Leptin, 16- kDa protein produced and secreted from white adipocytes is known to regulate food intake and energy expenditure. Leptin receptors have been detected in the pancreas and it has been shown that systemic application of this protein diminished postprandial pancreatic secretion. Leptin is also produced in the stomach and released into the gastrointestinal lumen but the implication of luminal leptin in the regulation of pancreatic enzyme secretion has not been elucidated. The aim of our study was to evaluate the effects of intraduodenal (i.d.) leptin administration on pancreatic enzyme secretion and to assess the involvent of afferent nerves and CCK in above effects. The secretory studies were carried out on anaesthetized Wistar rats with acute pancreatic fistulae. Leptin was administered to the animals at doses of 0.1 1.0 or 10.0 µg/kg i.d. Tarazepide (2.5 mg/kg i.d.), a CCK1 receptor antagonist, was given to the rats prior to the application of leptin. Rats with capsaicin deactivated sensory nerves were used in part of the study. Samples of pancreatic juice were taken at 15 min intervals to measure the volume flow and protein and amylase concentrations. CCK plasma level was measured by radioimmunoassay (RIA) following administration of leptin to the rats. Intraduodenal administration of leptin (1.0 or 10.0 µg/kg) to the fasted rats significantly and dose-dependently increased pancreatic protein and amylase outputs. Pancreatic secretory responses to leptin were totally abolished by prior capsaicin deactivation of sensory nerves or by pretreatment of the rats with tarazepide. Under basal conditions plasma CCK level averaged about 15.46 ± 1,4 pg/ml. Exogenous leptin, given i.d. at doses of 0.1 1.0 or 10.0 µg/kg i.d. to the rats with intact or capsaicin-deactivated sensory nerves resulted in dose-dependent rise of plasma CCK level, reaching the highest value at the dose of 10.0 µg/kg i.d. We conclude that leptin given i.d. stimulates pancreatic enzyme secretion and this effect could be related to the stimulation of CCK release and activation of duodeno-pancreatic reflexes.

4

Involvement of vagal nerves in the pancreatostimulatory effects of luminal melatonin, or its precursor L-tryptophan. Study in the rats

64%

Nawrot-Porabka K., Jaworek J., Leja-Szpak A., Szklarczyk J., Kot M., Mitis-Musiol M., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology. Supplement

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2007

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tom 58

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nr 6

5

Melatonin as modulator of pancreatic enzyme secretion and pancreatoprotector

64%

Jaworek J., Nawrot-Porabka K., Leja-Szpak A., Bonior J., Szklarczyk J., Kot M., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology. Supplement

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2007

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tom 58

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nr 6

6

The dynamics of heat shock system activation in Monomac-6 cells upon Helicobacter pylori infection

64%

Pierzchalski P., Jastrzebska M., Link-Lenczowski P., Leja-Szpak A., Bonior J., Jaworek J., Okon K., Wojcik P.

Journal of Physiology and Pharmacology

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2014

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tom 65

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nr 6

7

Kynuramines induce overexpression of heat shock proteins in pancreatic cancer cells via 5-hydroxytryptamine and melatonin MT1/MT2 receptors

64%

Leja-Szpak A., Pierzchalski P., Goralska M., Nawrot-Porabka K., Bonior J., Link-Lenczowski P., Jastrzebska M., Jaworek J.

Journal of Physiology and Pharmacology

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2015

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tom 66

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nr 5

8

Modulation of pancreatic enzyme secretion by melatonin and its precursor; L-tryptophan. Role of CCK and afferent nerves

64%

Leja-Szpak A., Jaworek J., Nawrot-Porabka K., Palonek M., Mitis-Musiol M., Dembinski A., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology. Supplement

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2004

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tom 55

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nr 2

33-46

Melatonin, a pineal hormone, is also produced in the gastrointestinal tract. Melatonin receptors have been detected in the stomach, intestine and pancreas. This indole inhibits insulin secretion but its role in the physiological modulation of exocrine pancreatic function is yet unknown. The aim of this study was to evaluate the pancreatic secretory effect of melatonin and its precursor; L-tryptophan given intraduodenally (i.d.) to the conscious rats with intact or capsaicin deactivated sensory nerves. CCK1 receptor antagonist; tarazepide, was used in the part of the study to determine the involvement of CCK in the secretory effects of melatonin. The secretory studies were performed on awaken rats surgically equipped with silicone catheters, one of them was inserted into pancreato-biliary duct, the other one - into duodenum. Melatonin (1, 5 or 25 mg/kg) or L-tryptophan (10, 50 or 250 mg/kg) were administered i.d. Samples of pancreatic juice were collected in 15 minutes aliquots. Tarazepide (2,5 mg/kg i.p.) was given to the rats 15 min prior to the administration of melatonin or L-tryptophan. Neurotoxic dose of capsaicin (100 mg/kg s.c.) was used to deactivate afferent nerves and thus to assess the role of these nerves in the melatonin-induced pancreatic enzyme secretion. Administration of melatonin (1, 5 or 25 mg/kg i.d.) or L-tryptophan (10, 50 or 250 mg/kg i.d.) significantly increased pancreatic amylase outputs. Deactivation of sensory nerves by capsaicin or administration of CCK1 - receptor antagonist; tarazepide, reversed the stimulatory effects of melatonin or L-tryptophan on pancreatic secretory function. Administration of melatonin or its amino-acid precursor to the rats resulted in the significant and dose-dependent rises of melatonin and CCK plasma levels. We conclude that melatonin or its precursor; L-tryptophan stimulates pancreatic enzyme secretion via stimulation of CCK release and activation of duodeno-pancreatic reflexes.

9

Effect of neonatal endotoxemia on the pancreas of adult rats

64%

Jaworek J., Leja-Szpak A., Nawrot-Porabka K., Bonior J., Szklarczyk J., Kot M., Konturek S. J., Tomaszewska R., Pawlik W. W.

Journal of Physiology and Pharmacology. Supplement

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2008

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tom 59

|

nr 4

87-102

10

Effect of central administration of L-tryptophan [melatonin precursor] and luzindole [melatonin MT2 receptor antagonist] on the course of caerulein induced acute pancreatitis in the rat

64%

Nawrot K., Jaworek J., Bonior J., Leja-Szpak A., Kot M., Sendur R., Pawlik W. W., Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2001

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tom 52

|

nr 2

11

Role of endogenous melatonin and its MT2 receptor in the modulation of caerulein-induced pancreatitis in the rat

64%

Jaworek J., Konturek S. J., Leja-Szpak A., Nawrot K., Bonior J., Tomaszewska R., Stachura J., Pawlik W. W.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 4,2

The present study investigated the involvement of endogenous melatonin in the prevention of pancreatic damage provoked by caerulein-induced pancreatitis (CIP) by using the luzindole, the antagonist of melatonin MT2 receptors. CIP was produced by subcutaneous infusion of caerulein to conscious rats (25 µg/kg). Luzindole (1, 2 or 4 mg/kg) was given as an intraperitoneal bolus injection 30 min prior to the start of CIP. Lipid peroxidation products, malondialdehyde (MDA) and 4- hydroxynonenal (4-HNE) were measured in the pancreas by LPO-584 commercial kit. CIP was confirmed by histological examination and manifested by significant increases of plasma activities of amylase, lipase and tumor necrosis factor a (TNFalpha) (by 500%, 1000% and 600%, respectively) comparing to the control values. This was accompanied by a 40% limitation in pancreatic blood flow (PBF) and by 200% increase of MDA+4-HNE in the pancreas of CIP rats. Administration of luzindole to the CIP rats reduced PBF, aggravated the histological manifestations of pancreatitis, resulted in the significant augmentation of pancreatic MDA + 4-HNE content, and produced the marked increases of plasma levels of lipase, amylase and TNFalpha, comparing to the values observes in the rats with CIP alone. These results suggest that endogenous melatonin through its receptor MT2 plays an important role in the attenuation of pancreatic damage produced by overstimulation with caerulein.

12

Sensory nerves in central and peripheral control of pancreatic integrity by leptin and malatonin

64%

Jaworek J., Bonior J., Leja-Szpak A., Nawrot K., Kot M., Tomaszewska R., Stachura J., Pawlik W. W., Konturek S. J.

Journal of Physiology and Pharmacology

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2002

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tom 53

|

nr 1

Central nervous system affects pancreatic secretion of enzymes however,the neural modulation of acute pancreatitis has not been investigated.Leptin and melatonin have been recently reported to affect the inflammatory response of various tissues.The identification of specific receptors for both peptides in the pancreas suggests that leptin and melatonin could contribute to the pancreatic protection against inflammation.The aim of this study was:1/to compare the effect of intracerebroventricular (i.c.v.)or intraperitoneal (i.p.) administration of leptin or melatonin on the course of caerulein-induced pancreatitis (CIP) in the rat,2/to examine the involvement of sensory nerves (SN)and calcitonin gene-related peptide (CGRP)in pancreatic protection afforded by leptin or melatonin,3/to assess the effect of tested peptides on lipid peroxidation products (MDA +4-HNE)in the pancreas of CIP rats,4/to investigate the influence of leptin or melatonin on nitric oxide (NO)release from isolated pancreatic acini and 5/to determine the effects of caerulein and leptin on leptin receptor gene expression in these acini by RT-PCR.CIP was induced by subcutaneous (s.c.)infusion of caerulein (25 µg/kg)to the conscious rats,confirmed by the significant increases of pancreatic weight and plasma amylase and by histological examination.This was accompanied in marked reduction of pancreatic blood flow and significant rise of MDA +4-HNE in the pancreas.Leptin or melatonin were administered i.p.or i.c.v.30 min prior to the start of CIP.Deactivation of SN was produced by s.c.capsaicin (100 mg/kg).An antagonist of CGRP,CGRP8-37 (100 µg/kg i.p.),was given together with leptin or melatonin to the CIP rats.MDA +4-HNE was measured using LPO commercial kit.NO was determined using the Griess reaction.Pretreatment of CIP rats with i.p.leptin (2 or 10 µg/kg)or melatonin (10 or 50 mg/kg)significantly attenuated the severity of CIP.Similar protective effects were observed following i.c.v.application of leptin (0.4 or 2 µg/rat)but not melatonin (10 or 40 µg/rat)to the CIP rats.Capsaicin deactivation of SN or administration of CGRP8-37 abolished above beneficial effects of leptin on CIP,whereas melatonin-induced protection of pancreas was unaffected.Pretreatment with i.p.melatonin (10 or 50 mg/kg),but not leptin,significantly reduced MDA +4-HNE in the pancreas of CIP rats.Leptin (10–9 -10–6 M)but not melatonin (10–8 -10–5 M)significantly stimulated NO release from isolated pancreatic acini.Leptin receptor gene expression in these acini was significantly increased by caerulein and leptin. We conclude that 1/central or peripheral pretreatment with leptin protects the pancreas against its damage induced by CIP,whereas melatonin exerts its protective effect only when given i.p.,but not following its i.c.v.adminstration,2/activation of leptin receptor in the.pancreatic acini appears to be involved in the beneficial effects of leptin on acute pancreatitis, 3/the protective effects of leptin involve sensory nerves,CGRP and increased generation of NO whereas melatonin-induced protection of the pancreas depends mainly on the antioxidant local effect of this indole,and scavenging of the radical oxygen species in the pancreatic tissue.

13

Exposition of newborn rats to bacterial endotoxin impairs pancreatic enzyme secretion at adult age

64%

Jaworek J., Nawrot-Porabka K., Leja-Szpak A., Szklarczyk J., Macko M., Bonior J., Stachura J., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology

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2007

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tom 58

|

nr 2

Lipopolysaccharide (LPS, endotoxin) is the component of the cellular wall of Gram negative bacteria. Endotoxemia (sepsis) could produce multiorgan failure and in the early period of life LPS are responsible for the changes of metabolism and for the reduction of protein synthesis. The influence of neonatal endotoxemia on the pancreas at adults has not been investigated yet. The aim of this study was to assess the pancreatic exocrine function in the adult rats which have been subjected, in the neonatal period of life, to chronic LPS pretreatment. LPS from E. coli or S. typhi at doses of 5, 10 or 15 mg/kg-day was administered intraperitoneally (i.p.) to the suckling rats (30 g) during 5 consecutive days. Three months later these animals (300 g) were equipped with pancreato-biliary fistulae for the in vivo secretory study. Amylase release from isolated pancreatic acini obtained from these rats was also assessed. Pancreatic tissue samples were taken for histological assessment and for the determination of gene expression for CCK1 receptor by RT-PCR. Pancreatic amylase secretions stimulated by caerulein or by diversion of pancreatic-biliary juice to the exterior (DBPJ) was significantly, and dose-dependently reduced in the adult rats which have been subjected in infancy to chronic pretreatment with LPS from E. coli or S. typhi, as compared to the untreated control. In these animals basal secretion was unaffected. In the rats pretreated with LPS in the suckling period of life caerulein-induced amylase release from isolated pancreatic acini was significantly decreased, as compared to the untreated with LPS control. This was accompanied by dose-dependent reduction of mRNA signal for CCK1 receptor on pancreatic acini. Neonatal endotoxemia failed to affect significantly pancreatic morphology as well as plasma amylase level in the adult rats. We conclude that neonatal endotoxemia reduces gene expression for CCK1 receptor and could produce impairment of the exocrine pancreatic function at adult age.

14

Leptin is involved in the protective effect of lipopolysaccharide [LPS] in the caerulein-induced pancreatitis

64%

Bonior J., Jaworek J., Leja-Szpak A., Nawrot K., Kot M., Bielanski W., Sendur R., Pawlik W. W., Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2001

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tom 52

|

nr 2

15

Endotoxemia in newborn rats attenuates acute pancreatitis at adult age

52%

Jaworek J., Konturek S. J., Macko M., Kot M., Szklarczyk J., Leja-Szpak A., Nawrot-Porabka K., Stachura J., Tomaszewska R., Siwicki A., Pawlik W. W.

Journal of Physiology and Pharmacology

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2007

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tom 58

|

nr 1

Bacterial endotoxin (lipopolysaccharide, LPS), at high concentration is responsible for sepsis, and neonatal mortality, however low concentration of LPS protected the pancreas against acute damage. The aim of this study was to investigate the effect of exposition of suckling rats to LPS on the course of acute pancreatitis at adult age. Suckling rat (30-40g) received intraperitoneal (i.p.) injection of saline (control) or LPS from Escherichia coli or Salmonella typhi (5, 10 or 15 mg/kg-day ) during 5 consecutive days. Two months later these rats have been subjected to i.p. caerulein infusion (25 µg/kg) to produce caerulein-induced pancreatitis (CIP). The following parameters were tested: pancreatic weight and morphology, plasma amylase and lipase activities, interleukin 1ß (IL-1 ß), interleukin 6 (IL-6), and interleukin 10 (IL-10) plasma concentrations. Pancreatic concentration of superoxide dysmutase (SOD) and lipid peroxidation products; malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) have been also measured. Caerulein infusion produced CIP in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS at doses 10 or 15 mg/kg-day x 5 days, all manifestations of CIP have been reduced. In these animals acute inflammatory infiltration of pancreatic tissue and pancreatic cell vacuolization have been significantly diminished. Also pancreatic weight, plasma lipase and a-amylase activities, as well as plasma concentrations of IL-1ß and IL-6 have been markedly decreased, whereas plasma anti-inflammatory IL-10 concentration was significantly increased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in pancreatic SOD concentration was reversed and accompanied by significant reduction of MDA + 4 HNE in the pancreatic tissue. The effects of LPS derived from E.coli or S.typhi were similar. Pretreatment of suckling rats with LPS at dose of 10 mg/kg-day x 5 days resulted in the most prominent attenuation of acute pancreatitis at adult age, whereas LPS at dose of 5 mg/kg-day x 5 days given to the neonatal rats failed to affect significantly acute pancreatitis induced in these animals 2 months later. We conclude that: 1/ Prolonged expositon of suckling rats to bacterial endotoxin attenuated acute pancreatitis induced in these animals at adult age. 2/ This effect could be related to the increased concentration of antioxidative enzyme SOD in the pancreatic tissue and to the modulation of cytokines production in these animals.

16

Melatonin precursor, L-tryptophan protects the pancreas from development of acute pancreatitis through the central site of action

52%

Leja-Szpak A., Jaworek J., Tomaszewska R., Nawrot K., Bonior J., Kot M., Palonek M., Stachura J., Czupryna A., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology

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2004

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tom 55

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nr 1,2

Melatonin, produced from L-tryptophan, protects the pancreas against acute damage by improving the antioxidative status of tissue. Melatonin receptors have been detected in the brain, but the contribution of these receptors to the pancreatic protection is unknown. The aim of our study was to compare the effects of melatonin precursor; L-tryptophan given intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) on the course of acute pancreatitis. Acute pancreatitis was induced by subcutaneous infusion of caerulein (5µg/kg-h x 5h). L-tryptophan was given i.p. (2.5, 25 or 250 mg/kg) or administered into right cerebral ventricle (0.02, 0.2 or 2.0 mg/rat) 30 min prior to the start of caerulein infusion. Plasma amylase, lipase and TNF alpha activities were measured to determine the severity of caerulein-induced pancreatitis (CIP). The lipid peroxidation products: malonylodialdehyde and 4-hydroksynonenal (MDA + 4-HNE) and activity of superoxide dismutase (SOD) were measured in the pancreas of intact or CIP rats with or without L-tryptophan pretreatment. Melatonin blood level was measured by RIA. CIP was confirmed by histological examination and manifested as an edema and rises of plasma levels of amylase, lipase and TNF alpha (by 550%, 1000% and 600%). MDA + 4-HNE was increased by 600%, whereas SOD activity was reduced by 75% in the pancreas of CIP rats. All manifestations of CIP were significantly reduced by pretreatment of the rats with L-tryptophan given i.c.v. at doses of 0.2 or 2.0 mg/rat, or by peripheral administration of this amino acid used at dose of 250 mg/kg i.p. In control rats plasma level of melatonin averaged about 40 ± 2 pg/ml and was not significantly affected by CIP, by central application of L-tryptophan (0.02, 0.2 or 2.0 mg/rat) or by peripheral administration of this melatonin precursor used at doses of 2.5 or 25 mg/kg i.p. Plasma melatonin level was markedly increased by pretreatment of the rats with L-tryptophan given i.p. at dose of 250 mg/kg. We conclude that central administration of melatonin precursor; L-tryptophan, as well as peripheral application of high dose of this melatonin precursor prevented the pancreatic damage produced by CIP. The favorable effect of peripherally administered L-tryptophan could be related to the rise of melatonin plasma level and to pancreatoprotective action of this indoleamine. The beneficial effect of centrally administered L-tryptophan could be mediated through activation of central receptors for locally produced melatonin.

Ograniczanie wyników

Brain-gut axis in the modulation of pancreatic enzyme secretion

Melatonin stimulates HSP27 phosphorylation in human pancreatic carcinoma cells [PANC-1]

Leptin is able to stimulate pancreatic enzyme secretion via activation of duodeno-pancreatic reflex and CCK release

Involvement of vagal nerves in the pancreatostimulatory effects of luminal melatonin, or its precursor L-tryptophan. Study in the rats

Melatonin as modulator of pancreatic enzyme secretion and pancreatoprotector

The dynamics of heat shock system activation in Monomac-6 cells upon Helicobacter pylori infection

Kynuramines induce overexpression of heat shock proteins in pancreatic cancer cells via 5-hydroxytryptamine and melatonin MT1/MT2 receptors

Modulation of pancreatic enzyme secretion by melatonin and its precursor; L-tryptophan. Role of CCK and afferent nerves

Effect of neonatal endotoxemia on the pancreas of adult rats

Effect of central administration of L-tryptophan [melatonin precursor] and luzindole [melatonin MT2 receptor antagonist] on the course of caerulein induced acute pancreatitis in the rat

Role of endogenous melatonin and its MT2 receptor in the modulation of caerulein-induced pancreatitis in the rat

Sensory nerves in central and peripheral control of pancreatic integrity by leptin and malatonin

Exposition of newborn rats to bacterial endotoxin impairs pancreatic enzyme secretion at adult age

Leptin is involved in the protective effect of lipopolysaccharide [LPS] in the caerulein-induced pancreatitis

Endotoxemia in newborn rats attenuates acute pancreatitis at adult age

Melatonin precursor, L-tryptophan protects the pancreas from development of acute pancreatitis through the central site of action