Biomedical subjects

Z Warzecha

Publications and source records attributed to Z Warzecha.

At least 37 records · Page 2Linked to original sources

PubMed2000

Morphological changes and morphological-functional correlations in acute experimental ischemia/reperfusion pancreatitis in rats.

The etiology of acute pancreatitis, apart from alcohol abuse and cholelithiasis may also include a vascular component responsible for pancreatic ischemia. It is now acknowledged that chronic pancreatitis may be a consequence of the acute variant, but it remains unclear what factors influence this sequence of morphological changes. In order to clarify this issue we proposed a model of experimental acute pancreatitis in rats induced by a 30 min reduction of blood flow in inferior splenic artery followed by reperfusion. Rats were sacrificed at 1 h, 12 h, 24 h, and 2, 3, 5, 7, 14, 21, 28 days after cessation of ischemia. We performed histopathological examination of pancreatic tissue and measured pancreatic blood flow, plasma amylase activity and interleukin-1 beta concentration. The present findings indicate that transient pancreatic ischemia leads to the development of acute necro-haemorrhagic pancreatitis. The morphological features of acute inflammation are correlated positively with functional disorders. In some cases the features of chronic pancreatitis may appear transiently after the acute phase, whereas the repair of postinflammatory injury involves the regeneration of acinar cells.

Acute Disease↗

PubMed1999

Calcitonin gene-related peptide can attenuate or augment pancreatic damage in caerulein-induced pancreatitis in rats.

UNLABELLED: We have recently shown that treatment with calcitonin gene-related peptide (CGRP) before and during induction of acute pancreatitis exhibits a protective effect against pancreatic damage evoked by overdose of caerulein. Studies in the stomach have shown that administration of CGRP exhibits dual action on gastric mucosa, CGRP administration before induction of gastric lesions, protects gastric mucosa against damage, whereas treatment with this peptide after development of gastric ulcer exacerbates mucosal injury. These observations prompt us to determine the influence of CGRP administrated before and after induction of pancreatitis on development and evolution of pancreatic tissue damage. METHODS: Acute pancreatitis was induced by s.c. infusion of caerulein (10 microg/kg/h) for 5 h. CGRP was administrated (10 microg/kg s.c. per dose) 30 min prior to caerulein infusion and 3 h later during caerulein infusion or at the time 1 h, 4 h and 7 h after the end of caerulein infusion. Rats were sacrificed at the time 0 h, 3 h or 9 h after cessation of caerulein administration. The pancreatic blood flow (PBF), plasma activity of amylase, plasma interleukin-1beta concentration, cell proliferation, biochemical and morphological signs of pancreatitis were examined. RESULTS: Caerulein-induced pancreatitis (CIP) led to 42% decrease in DNA synthesis, 30% inhibition of PBF, as well as, a significant increase in pancreatic weight, plasma amylase activity, plasma interleukin-1beta concentration, and development of the histological signs of pancreatic damage (edema, leukocyte infiltration and vacuolization). Treatment with CGRP prior and during induction of CIP attenuated the pancreatic damage what was manifested by partial reversion of the drop in DNA synthesis (40.9+1.7 v. 34.2+2.0 dpm/microg DNA) and PBF (83+3% v. 70+3%). Increases in pancreatic weight and plasma interleukin-1beta were reduced. Morphology showed improvement of pancreatic integrity. Administration of CGRP after induction of CIP aggravated pancreatic damage what was manifested by additional decrease in PBF and DNA synthesis. Also pancreatic weight as well as histological signs of pancreatic damage were increased. CONCLUSIONS: (1) Administration of CGRP before and during induction of pancreatitis protects pancreas against pancreatic damage. (2) Treatment with CGRP after development of CIP aggravates pancreatic damage.

Animals↗

PubMed1998

Comparison of epidermal growth factor and transforming growth factor-beta1 expression in hormone-induced acute pancreatitis in rats.

Overexpression of transforming growth factors (TGF) in acute pancreatitis (AP) suggested that these substances play an important role in pancreatic repair and remodeling but the contribution of epidermal growth factor (EGF), that is well known to promote cell growth and regeneration, has not been investigated. The aim of this study was to compare the gene and immunohistochemical expression of EGF and TGF-beta1, cell proliferation, and biochemical parameters in AP induced by infusion of a supramaximal dose of caerulein in rats. The rats were sacrificed at 0, 12, 24, 48, 72 h, 5 and 10 days after the termination of caerulein infusion. Pancreatic tissue DNA synthesis, cell proliferation, histological and immunohistochemical assessments and plasma amylase were estimated following induction of AP. The mRNA expression for EGF and TGF-beta1 was evaluated by reverse transcription-polymerase chain reaction. During 10 days of the study after induction of AP a gradual normalization of biochemical and histological parameters was observed. DNA synthesis and cell proliferation which were significantly decreased at 0 and 24 h, increased significantly at 48 and 72 h, and then gradually decreased reaching at day 10 the values similar to those of vehicle-treated control rats. In these control rats the EGF mRNA or immunohistochemical expression was not detected, while the TGF-beta1 expression was weak. After induction of AP, the mRNA and immunohistochemical expression of EGF showed an increase during the initial 5 days, while those of TGF-beta1 showed a marked increase between 0 and 48 h and then again at day 10. We confirm that: (1) the expression of TGF-beta1 during AP is biphasic with an initial increase probably related to pancreatic damage and inhibition of cell proliferation and with the later phase of increase accompanied by the stimulation of the synthesis of extracellular matrix components and (2) AP is accompanied by an induction of synthesis of EGF that occurs in the initial phase of AP, probably limiting the extent of AP, and enhancing the stimulation of the pancreatic repair and regeneration.

Acute Disease↗

PubMed1997

Role of sensory nerves in pancreatic secretion and caerulein-induced pancreatitis.

Sensory nerves are implicated in gastroprotection and regulation of visceral circulation but their role in exocrine secretion and pancreatic circulation in intact pancreas and in acute pancreatitis has not been established. We investigated the role of sensory fibers in pancreatic secretion in vivo and amylase release from pancreatic slices (containing nerve fibers) or isolated pancreatic acini, and in caerulein-induced pancreatitis. In conscious rats, the stimulation of sensory nerves by low dose of capsaicin given intraduodenally (0.25-0.5 mg/kg) reduced basal pancreatic secretion, whereas dose of 1 mg/kg increased this secretion. Deactivation of sensory nerves by neurotoxic dose of capsaicin (100 mg/kg over 3 days s.c.) 10 days before tests failed to affect basal secretion but diminished the secretion induced by feeding or the diversion of pancreatic juice. In pancreatic slices, capsaicin (10(-10)-10(-6) M) increased enzyme secretion and this response was abolished by atropine (10(-6) M) or previous deactivation of sensory nerves. In pancreatic acini, capsaicin failed to affect basal and stimulated amylase secretion in response to caerulein or urecholine. In intact rats, stimulatory dose of capsaicin (0.5 mg/kg i.g.) caused about 32% increase of pancreatic blood flow and it was without any effect on the pancreatic DNA synthesis, weight, RNA, DNA and protein content. In contrast, neurotoxic dose of capsaicin caused a reduction (by 27%) in pancreatic blood flow followed by a significant decrease in RNA content and DNA synthesis in pancreatic tissue. Infusion of caerulein (10 g/kg-h) for 5 h produced acute edematous pancreatitis accompanied by over 60% decrease in DNA synthesis, nearly 50% inhibition of pancreatic blood flow, and a significant increase in pancreatic weight, protein content and plasma amylase concentration. Stimulatory dose of capsaicin attenuated the pancreatic tissue damage in caerulein induced pancreatitis, as manifested by a significant reversal of pancreatic blood flow and DNA synthesis decrease. Capsaicin induced inactivation of sensory nerves prior to pancreatitis caused an increase of all parameters of pancreatic damage; pancreatic blood flow dropped by 68%, DNA synthesis decreased by 70%; pancreatic weight, protein content and plasma amylase were also significantly enhanced. We conclude that sensory neurons are involved in the regulation of pancreatic secretion by an indirect mechanism and exhibit a beneficial effect on the pancreatic integrity, mainly due to improving the pancreatic blood flow.

Amylases↗

PubMed1997

Expression of transforming growth factor-beta 1 and epidermal growth factor in caerulein-induced pancreatitis in rat.

Growth factors such as TGF-beta 1 and EGF are known to modulate the deposition of extracellular matrix components and tissue repair and to affect the cellular growth but their expression in the course of pancreatitis has not been studied. In this study we investigated the gene expression of TGF-beta 1 mRNA and EGF mRNA and other parameters of the pancreas including DNA synthesis, blood flow (PBF), tissue protein content and plasma amylase during the induction of acute pancreatitis. Supramaximal dose of cearulein (10 mg/kg/h s.c.) was infused for 5 h to induce pancreatitis. Animals were killed after 1, 2, 3, 4 and 5 h of infusion. The PBF was measured, blood samples were withdrawn to determine serum amylase concentration, biopsy samples were taken to measure the protein content and DNA synthesis. Expression of TGF-beta 1 and EGF mRNA was studied by reverse-transcription of polymerase chain reaction (RT-PCR). Caerulein infused caused a time-dependent decrease in DNA synthesis accompanied by gradual decrease of PBF and significant increase in pancreatic weight. The pancreatic protein content and plasma amylase showed progressive rise during 5 h of cearulein infusion. Histology revealed tissue edema, cellular vacuolization and prominent leukocyte infiltration after 3 h of cearulein infusion. TGF-beta 1 mRNA was strongly expressed at each time interval beginning from the 1 h after the start of cearulein infusion. In contrast, EGF mRNA was detected only at 5 h after induction of pancreatitis. We conclude that 1) the development of caerulein-induced pancreatitis results in the inhibition of pancreatic growth and the reduction in PBF accompanied by enhanced expression of TGF-beta 1; 2) The expression of EGF that was observed at the end of the induction of pancreatitis may indicate the initiation of pancreatic repair; 3) TGF-beta 1 seems to lead to subsequent induction of EGF that may stimulate the regeneration of injured pancreas.

Acute Disease↗

PubMed1997

Adaptation of the pancreas to repeated caerulein administration in rats. A morphological and functional study.

We studied the ability of the pancreas in the aspect of histological, biochemical and functional changes (pancreatic blood flow, serum and pancreatic amylase levels, DNA and RNA content and pancreatic mass) to recover from repeated episodes of caerulein-induced acute pancreatitis. The experiment was carried out in three animal groups: group I receiving one infusion of caerulein, group II receiving two infusions of caerulein at the interval of 10 days, and group III with three infusions every 10 days. It was found that histological signs of acute pancreatitis after the first caerulein infusion showed regression after 3 days, and the process of regeneration was almost completed after 10 days. The content of DNA and RNA correlated with the histological picture. At this time interval also the level of amylase was returning to normal. Each subsequent infusion of caerulein resulted in less enhanced tissue destruction, but regeneration started later. Pancreatic blood flow was decreased each time after induction of pancreatitis, whereas normalization was more rapid. The present findings indicate that the pancreas adapts to repeated injury, which is manifested by decreased severity of changes, but the process of regeneration is delayed.

Adaptation, Physiological↗

PubMed1997

Protective effect of calcitonin gene-related peptide against caerulein-induced pancreatitis in rats.

The stimulation of sensory nerves by capsaicin exhibits the protective effect against caerulein-induced pancreatitis whereas deactivation of these nerves aggravates pancreatic damage evoked by overdose of caerulein. Calcitonin-gene related peptide (CGRP) has been identified as the prominent mediator of sensory nerves. The aim of the present study was to examine the influence of CGRP on the course of caerulein-induced pancreatitis (CIP). CIP led to a significant decrease in DNA synthesis and pancreatic blood flow (PBF) by 48% and 50% respectively, as well as a significant increase of pancreatic weight, plasma amylase concentration and development of the histological signs of pancreatic damage expressed as edema, leukocyte infiltration and vacuolization. Treatment with CGRP (2 x 10 micrograms/kg s.c.) attenuated the pancreatic tissue damage in caerulein-induced pancreatitis and completely reversed the deleterious effect of the ablation of sensory nerves on caerulein-induced pancreatitis. We conclude that CGRP exerts protective effect against caerulein-induced pancreatitis and is able to reverse the damage caused by deactivation of sensory nerves. Vasodilatation and preservation of pancreatic blood flow are involved in this effect.

Amylases↗

PubMed1996

Influence of capsaicin-sensitive afferent neurons and nitric oxide (NO) on cerulein-induced pancreatitis in rats.

CONCLUSION: Stimulation of afferent neurons by capsaicin exerts protective activity against cerulein-induced pancreatitis. This action is dependent on endogenous release of nitric oxide (NO). Deactivation of afferent neurons by high doses of capsaicin contributes to the severity of pancreatitis. This action involves mainly decreased pancreatic blood flow (PBF). Afferent nerves and NO cooperate in the maintenance of the integrity of pancreatic tissue. BACKGROUND: Stimulation of capsaicin-sensitive afferent fibers protects gastric mucosa against damage and causes changes in mucosal blood flow. The aim of the present study was to determine the role of stimulation or ablation of capsaicin-sensitive neurons and NO in the course of cerulein-induced pancreatitis in the rat. METHODS: Low and high doses of capsaicin were administered to animals with pancreatitis and to those without pancreatitis. The effect of several parameters was assessed. NO activity was blocked by NG-nitro-L-arginine. RESULTS: We found that a low dose of capsaicin administered intragastrically caused an increase in PBF. A neurotoxic dose of capsaicin caused a decrease in PBF, RNA content, and DNA synthesis. Pancreatitis led to a significant decrease in PBF and DNA synthesis, but an increase in pancreatic weight, protein content, plasma amylase concentration, and neutrophil adherence. Stimulatory doses of capsaicin attenuated the pancreatic tissue damage of pancreatitis, and alteration of PBF, DNA synthesis, and neutrophil adherence. Capsaicin-induced ablation of afferent neurons caused an increase in all indicators of pancreatic damage. Blocking NO enhanced pancreatic damage, and this was reversed by addition of L-arginine.

Animals↗

PubMed1996

Adaptation of pancreas to repeated caerulein-induced pancreatitis in rats.

Induction by caerulein of acute pancreatitis with tissue damage and acinar cells loss is followed by recovery. We studied biochemical, histological and functional regeneration of pancreatic tissue after repeated acute pancreatitis. Pancreatitis was evoked in rats by s.c. infusion of caerulein (10 micrograms/kg/h) for 5 h. After infusion, rats were divided into three groups. First group was infused with caerulein one time, in the second group infusion of caerulein was repeated 10 days later. The third groups was infused with caerulein for the 3rd time 10 days after the 2nd infusion. Rats were sacrificed at time sequence of 0, 12, 24, 48, 72 hours and at 5th, and 10th day after last infusion of caerulein. Pancreatic blood flow (PBF) was measured using laser Doppler flowmeter. Plasma and pancreatic amylase, pancreatic weight, RNA and DNA contents, and histological changes were determined. We found that DNA and RNA content, as well, as histological changes in 1st group showed progressive regeneration after 3 days. Regeneration after 1st time caerulein-induced pancreatitis was almost completed within 10 days and amylase content in the tissue and plasma amylase level returned to normal values. Each subsequent infusion of caerulein caused significantly less pronounced destruction of the pancreatic tissue, however, the regeneration occurred progressively later than after the 1st or 2nd infusion. Tissue repair after the 2nd infusion reached peak at 5th day while after 3rd infusion at 10th day. PBF dropped after 1st caerulein induced pancreatitis by about 50% but with repeated caerulein induced pancreatitis lower decreases in PBF were observed and they returned in shorter time back to control value. These results indicate that the pancreas is able to adapt to repeated injury and this is manifested by cumulative decrease of pancreatic damage after each repetition of induction of acute pancreatitis and correlated with the preservation of PBF, however, the pancreatic tissue regeneration is significantly delayed.

Acute Disease↗

PubMed1995

Gastric adaptation to stress: role of sensory nerves, salivary glands, and adrenal glands.

BACKGROUND: Single exposure to water immersion and restraint stress (WRS) in rats produces acute gastric mucosal damage, but repetitive WRS insults lead to gastric adaptation to stress ulcerogenesis. This study was designed to assess the mechanism of this adaptation, particularly the role of sensory nerves, salivary glands, adrenal glands, and gastric acid secretion. METHODS: WRS was applied for a standard period of 3.5 h, either once or repeated every other day for up to 8 days in intact rats and in animals with capsaicin-induced deactivation of sensory nerves, vagotomy, salivectomy, adrenalectomy, and inhibition of gastric acid secretion by H2-blocker. RESULTS: WRS applied once produced multiple gastric erosions accompanied by a significant increase in gastric acid secretion and a decrease in gastric blood flow (GBF) and DNA synthesis. Repeated WRS insults resulted in a significant decrease in the number of gastric lesions, reaching a maximum after four consecutive exposures to WRS. This adaptation to stress ulcerogenesis was accompanied by a decrease in gastric acid secretion and an increase in GBF and mucosal generation of DNA synthesis. Salivectomy, which decreased the luminal content of epidermal growth factor (EGF) (by about 80%), markedly attenuated this adaptation, and this was reversed by the addition of exogenous EGF. Capsaicin-induced ablation of sensory nerves eliminated gastric adaptation to WRS, and this was accompanied by a significant decrease in the GBF, but pretreatment with calcitonin gene-related peptide restored gastric adaptation to stress in capsaicin-denervated rats. Selective vagotomy and adrenalectomy failed to affect gastric adaptation to WRS, whereas gastric acid inhibition by ranitidine enhanced this adaptation. CONCLUSIONS: The stomach is able to adapt to repeated stress insults by enhancing GBF and DNA synthesis, and this adaptation is mediated, at least in part, by sensory nerves and EGF.

Adaptation, Physiological↗

PubMed1995

The role of capsaicin-sensitive sensory neurons and nitric oxide in regulation of gastric mucosal growth.

Capsaicin and nitric oxide (NO) cause potent vasorelaxation which is important in gastroprotective activity against damage but the mechanisms underlying these effects have not been elucidated. This study investigated the influence of capsaicin-induced functional ablation of afferent neurons and inhibition of NO production on the gastric mucosal growth in normal conditions, after 48 h fasting and subsequent refeeding. We found that ablation of sensory neurons by capsaicin pretreatment (100 mg/kg over 3 days) reduced by around 45% the mucosal blood flow (MBF), as measured by laser Doppler flowmetry, in normal fed and refed rats, while by 15% only in fasted animals. This last group of animals had significant decrease in the MBF even in control conditions as compared to that recorded in fed animals. This drop in MBF after capsaicin-induced denervation was accompanied by a significant decrease in DNA synthesis (by 40% in control group and 35% in refed rats) and was less pronounced in the group of fasted rats (23%). Ablation of sensory neurons resulted in the decrease in the stomach weight and RNA content in regular feed and refed but not in 48 h fasted group of animals. Treatment with NG-nitro-L-arginine (L-NNA; 2 x 20 mg/kg daily s.c.), a selective blocker of NO synthase, significantly suppressed the MBF in all three groups of animals tested but this suppression was less pronounced when compared to capsaicin pretreatment. This inhibitory effect of L-NNA on MBF was fully antagonized by L-arginine (2 x 100 mg/kg daily s.c.). L-NNA injection s.c. reduced the DNA synthesis (36% control group, 38% refed animals, 18% fasted rats), stomach weight, RNA and DNA content in all tested groups of rats. This inhibition was reversed by the addition of L-arginine. The combination of capsaicin and L-NNA decreased the MBF significantly and the inhibition was stronger than the effect of each substance given alone. In normal fed and refed rats, the neurotoxic dose of capsaicin together with L-NNA significantly decreased the DNA synthesis, stomach weight, RNA and DNA content but these effects were smaller than the sum of the effects of each agent given alone. We conclude that both the capsaicin-induced denervation and the suppression of endogenous NO by L-NNA inhibit the growth of the gastric mucosa by the mechanism involving, at least in part, the suppression of gastric mucosal blood flow.

Animals↗

PubMed1994

Nitric oxide in pancreatic secretion and hormone-induced pancreatitis in rats.

The aim of the present study was to determine the role of endogenous nitric oxide (NO) in pancreatic secretion in vivo and amylase release from pancreatic acini in vitro and in caerulein-induced acute pancreatitis in rats. Blockade of NO synthase by NG-nitro-L-arginine (L-NNA) (2.5 mg/kg i.v.) significantly reduced basal pancreatic protein secretion and that induced by the infusion of CCK (0.5 micrograms/kg-h), feeding, and the diversion of pancreatic juice in rats with pancreatic fistula. This inhibitory effect was partially reversed when L-arginine (50 mg/kg-h i.v.) was added to L-NNA. L-Arginine alone (50 mg/kg i.v.) did not affect basal or caerulein-induced pancreatic secretion. L-NNA, L-arginine, or their combination added in various concentrations to the incubation medium of dispersed acini failed to affect basal or secretagogue (caerulein or urecholine) stimulated amylase release. Infusion of caerulein (5 micrograms/kg-h) for 5 h produced histological changes of acute edematous pancreatitis accompanied by a marked increase in pancreatic protein content and about 50% reduction in tissue blood flow. L-NNA alone also reduced the pancreatic blood flow and caused a significant increase in pancreatic weight and protein content. L-NNA significantly potentiated the inflammatory changes in the pancreas caused by caerulein. Addition of L-arginine enhanced the pancreatic blood flow and ameliorated the pancreatitis induced by caerulein alone or that combined with L-NNA. We conclude that NO is involved in the stimulation of pancreatic secretion in vivo and exhibits a beneficial effect on pancreatitis, probably by improving the pancreatic blood flow.

Amylases↗

PubMed1992

Role of platelet activating factor in pathogenesis of acute pancreatitis in rats.

The importance of platelet activating factor in acute pancreatitis was examined by determining the tissue content of endogenous platelet activating factor and the protective effects of TCV-309, a highly selective platelet activating factor blocker, against caerulein induced pancreatitis in rats. Infusion of caerulein (10 micrograms/kg/h) for five hours resulted in about 70% increase in pancreatic weight, 22% rise in protein content, 50% reduction in tissue blood flow, nine fold increase in tissue level of platelet activating factor and 165% rise in plasma amylase as well as histological evidence of acute pancreatitis. Such infusion of caerulein in chronic pancreatic fistula rats caused a marked increase in protein output from basal secretion of 10 mg/30 minutes to 40 mg/30 minutes in the first hour of infusion followed by a decline in protein output to 15-20 mg/30 minutes in the following hours of the experiment. Exogenous platelet activating factor (50 micrograms/kg) injected ip produced similar alterations in weight, protein content, blood flow, and histology of the pancreas but the increment in serum amylase was significantly smaller and pancreatic secretion was reduced below the basal level. TCV-309 (50 micrograms/kg) given ip before caerulein or platelet activating factor administration significantly reduced the biochemical and morphological alterations caused by caerulein and abolished those induced by exogenous platelet activating factor. These results indicate that platelet activating factor plays an important role in the pathogenesis of acute pancreatitis probably by reducing the blood flow and increasing vascular permeability in the pancreas.

Acute Disease↗

PubMed1992

Platelet activating factor (PAF) inhibitor (TCV-309) reduces caerulein- and PAF-induced pancreatitis. A morphologic and functional study in the rat.

Caerulein-induced acute pancreatitis was studied in rats. Consistent with this type of acute pancreatitis morphological (edema, leukocytic infiltration and acinar cell vaculization) and biochemical (increase in pancreatic protein content. PAF release and serum amylase) changes developed 5 hours after caerulein administration. In addition increase in pancreatic weight and decrease in pancreatic blood flow were noticed. PAF administration caused pancreatic damage similar in some parameters to caerulein-induced pancreatitis, along with reduction of pancreatic blood flow, increase in pancreatic protein content, and serum amylase. TCV-309, a selective PAF antagonist, administered prior to caerulein and/or PAF, reduced caerulein-induced pancreatitis and prevented PAF-induced pancreatitis. Results of our present studies indicate the crucial role of PAF in pathogenesis of experimental acute pancreatitis.

Acute Disease↗

PubMed1991

Antagonism of receptors for bombesin, gastrin and cholecystokinin in pancreatic secretion and growth.

The effects of bombesin, gastrin and cholecystokinin (CCK) on amylase secretion from the isolated rat pancreatic acini and on DNA synthesis (as biochemical indicator of trophic action) in the pancreas have been examined in 48-hour fasted and 16-hour refed rats with and without administration of specific receptor antagonists for bombesin, gastrin and CCK. Studies on the isolated rat acini revealed that bombesin, gastrin and CCK-8 all showed the same efficacy in their ability to stimulate amylase release. RC-3095, bombesin pseudo-peptide antagonizing bombesin receptors, was effective only in suppressing the amylase response to bombesin but not to gastrin or CCK. Benzodiazepine receptor antagonists for gastrin (L-365,260) and for CCK (L-364,718) showed higher efficacy in the inhibition of amylase release induced by pentagastrin and CCK, respectively, but failed to affect that induced by bombesin. These peptides administered 3 times daily for 48 h in fasted rats increased the rate of DNA synthesis as measured by the incorporation of [3H]thymidine into DNA. The blockade of bombesin receptors abolished the DNA synthesis induced only by bombesin but not by gastrin or CCK. The blockade of gastrin receptors by L-365,260 suppressed the DNA synthesis induced by gastrin while the antagonism of CCK receptors by L-364,718 was effective only against CCK. Refeeding of 48-hour fasting rats strongly enhanced DNA synthesis which was significantly reduced by blocking only the CCK receptors (with L-364,718), but not the bombesin (with RC-3095) or gastrin receptors (with L-365,260).(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

PubMed1991

The effects of antagonists of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas.

The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [3H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718 a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365,260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364,718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptor but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.

Animals↗

PubMed1991

The effect of antagonist of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas.

The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas, have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [3H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718, a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365, 260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364,718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptors, but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.

Animals↗

PubMed1989

Epidermal growth factor in the gastroprotective and ulcer-healing actions of sucralfate in rats.

Sucralfate exhibits gastroprotective properties in laboratory animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether or not epidermal growth factor (EGF), which also has gastroprotective and ulcer-healing properties, contributes to the action of sucralfate in rat stomach. It was confirmed that sucralfate, like 16,16-dimethyl prostaglandin E2, protects the gastric mucosa against ethanol damage and increases mucosal generation of prostaglandins. Removal of the endogenous source of EGF (sialoadenectomy) did not abolish the protective and prostaglandin-stimulating effects of sucralfate. Exogenous EGF and 16,16-dimethyl prostaglandin E2 were also protective in rats with intact and removed salivary glands. Sucralfate, like EGF, enhanced the healing of chronic gastric and duodenal ulcerations induced by serosal application of acetic acid. Sucralfate was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer areas. Thus, the peptide is available locally in high concentrations to accelerate tissue repair and the healing process in ulcerated mucosa. The ulcer-healing effects of sucralfate were reduced with sialoadenectomy and partially restored with oral administration of EGF. It was concluded that EGF is not essential for the gastroprotection induced by sucralfate, but seems to play an important role in the ulcer-healing action of this drug.

16,16-Dimethylprostaglandin E2↗