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1

Free fatty acid receptors and their physiological roles in the colon

100%
Karaki S. I., Kuwahara A.
Medycyna Weterynaryjna
|
2010
|
tom 66
|
nr 03
147-154
Free fatty acids (FFAs) are not only an important source of energy but they also play key roles in regulating various physiological responses. FFAs including short-chain fatty acids (SCFAs) have recently been demonstrated to act as ligands of several G-protein-coupled receptors (GPCRs) (FFA1, FFA2, FFA3, GPR84 and GPR120). FFA1 and GPR120 are activated by medium- and long chain fatty acids. GPR84 is activated by mediam-chain, but not long chain FFAs. On the other hand, FFA2 and FFA3 are both activated by SCFAs. Tissue distribution studies have indicated that FFA2 and FFA3 function as chemical sensors in the colon. For the involvement of SCFAs in the regulation of colonic motility, propionate and butyrate concentration- -dependently induced phasic and tonic contractions in rat colonic circular muscle. The responses were not observed in mucosal free preparation. Thus, FFA2 and FFA3 are important molecular devices to monitor the chemical composition in colonic lumen. For the local function of SCFAs, it should be stressed that individual SCFA has different mode of actions on colonic smooth muscles. These different effects may be due to the relative contribution of FFA2 and FFA3 on the control of intestinal muscle activity. In this article, we have reviewed the expression and functions of these molecules, especially FFA2 and FFA3 on the regulation of colonic motility.
2
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Cardiovascular effects of centrally acting orexin A in haemorrhage-shocked rats

71%
Jochem J., Zwirska-Korczala K., Zabielski R., Kato I., Kuwahara A.
Journal of Physiology and Pharmacology. Supplement
|
2006
|
tom 57
|
nr 11
115-124
Orexin A influences the central cardiovascular regulation, since after intracerebroventricular (icv) administration it evokes short-lasting increases in mean arterial pressure (MAP) and heart rate (HR) in normotensive animals. The aim of the present study was to examine haemodynamic effects of orexin A in haemorrhage-shocked rats. Experiments were carried out in anaesthetized Wistar rats subjected for a critical irreversible haemorrhagic hypotension of 20-25 mmHg, which resulted in the death of all saline icv-treated control animals within 30 min. Orexin A (0.5-1.5 nmol; icv) administered at 5 min of critical hypotension evoked dose-dependent long-lasting increases in MAP, HR and renal, mesenteric and hindquarters blood flows, with a 100% survival of 2 h after treatment (1.5 nmol; icv). Changes in MAP and peripheral haemodynamics were inhibited by intravenous pretreatment with alpha1- and alpha2-adrenoceptor antagonists prazosin (0.5 mg/kg) and yohimbine (1.0 mg/kg), respectively. Moreover, both antagonists significantly decreased the survival rate to 16.6 and 33.3% (P<0.05 vs. orexin A [1.5 nmol]-treated group). In contrast, ß-adrenoceptor antagonist propranolol (1.0 mg/kg) completely blocked orexin A-induced HR changes, without influence on MAP, peripheral blood flows and the survival rate. Therefore, we conclude that centrally acting orexin A evokes the resuscitating effect in haemorrhage-shocked rats due to the activation of the sympathetic nervous system.
3
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Role of feed-regulating peptides on pancreatic exocrine secretion

71%
Kapica M., Puzio I., Kato I., Kuwahara A., Zabielski R.
Journal of Physiology and Pharmacology. Supplement
|
2008
|
tom 59
|
nr 2
In recent two decades a group of feed intake-regulating peptides (i.e., leptin, apelin, ghrelin, obestatin and orexins) have been discovered. Besides the central nervous system these regulatory peptides are produced and released by the gastrointestinal (GI) endocrine cells and neurons, and functional receptors were found in the GI tract and the pancreas. High expression of feed intake-regulating peptides was found in the stomach; however, they may be expressed in other GI tissues too. The peptides control gastrointestinal functions, modulate orexigenic drive and energy metabolism via different mechanisms. Basal leptin, apelin, ghrelin and obestatin plasma concentrations correlated with BMI, and we observed significant reduction of ghrelin and leptin concentrations following fundectomy in rats. We have shown previously that exogenous leptin and ghrelin (a peptide derived from the same preprohormone as obestatin) inhibit the secretion of rat pancreatic juice through a neurohormonal mechanism. Intravenous obestatin was found to stimulate pancreatic protein output in anaesthetized rat via a CCK-vagal-dependent mechanism, whilst a direct action of obestatin on rat pancreatic acini in vitro resulted in opposite effect. Intravenous boluses of apelin reduced the juice volume, protein and trypsin outputs in a dose-dependent manner. However, apelin administered into the duodenal lumen significantly increased pancreatic protein and trypsin outputs through a vagal mechanism. Orexin A and B were found to stimulate insulin release, though on the rat exocrine pancreas orexin A had no effect, and the effect of orexin B was weak. Concluding, feed intake-regulating peptides participate in controlling the exocrine pancreas.
4

Effect of intravenous administration of glucagon-like peptide. I on growth hormone secretion in sheep

61%
Kurose Y., Kuwahara A., Oshiba Y., Takahashi H., Watanabe Y., Terashima Y.
Journal of Animal and Feed Sciences. Supplement
|
2004
|
tom 13
|
nr 1
5
Content available remote

The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats

61%
Antushevich H., Kapica M., Krawczynska A., Herman A., Kato I., Kuwahara A., Zabielski R.
Journal of Physiology and Pharmacology
|
2016
|
tom 67
|
nr 3
6

Exogenous obestatin affects pancreatic enzyme secretion in rat through two opposite mechanisms, direct inhibition and vagally-mediated stimulation

61%
Kapica M., Puzio I., Kato I., Kuwahara A., Zabielski R., Antushevich H.
Journal of Animal and Feed Sciences
|
2018
|
tom 27
|
nr 2
It is suggested that obestatin can stimulate the secretion of pancreatic juice in rats and this effect is abolished by vagotomy. Thus, the aim of the present study was to further elucidate the mechanism by which obestatin controls the exocrine pancreas secretion. Anesthetized male Wistar rats (200 ± 15 g body weight) were administered intravenously (iv) and intraduodenaly (id) every 30 min obestatin in boluses of 30, 100 and 300 nmol ∙ kg−1 body weight and 15 min later pancreatic-biliary juice (PBJ) was collected to determine the PBJ volume, total protein and enzymes activity. Obestatin injections were also done following subdiaphragmatic vagotomy, capsaicin deafferentation and pharmacological blockage of the mucosal cholecystokinin 1 (CCK1) receptor with tarazepide. Dispersed acinar cells were isolated from rat pancreas by collagenase digestion, stimulated with CCK-8 (10−10 M) and incubated with obestatin (10−9–10−6 M) in vitro. It was noted that iv and id obestatin administrations did not affect the PBJ volume but increased protein and trypsin outputs regardless way of administration, and amylase and lipase outputs after id injection. Similarly to vagotomy, the capsaicin and tarazepide pre-treatments abolished the effects of obestatin. In contrast to the in vivo experiment, the treatment of dispersed pancreatic cells with the CCK-8+obestatin combination showed that obestatin decreased the CCK-8-stimulated amylase release from acinar cells in vitro, but obestatin alone did not exert effect on amylase release. So, it is thought that obestatin can stimulate the exocrine pancreas secretion via an indirect vagal mechanism, whilst its direct action on the acinar cells is also possible but with the opposite effects
7
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Obestatin stimulates the secretion of pancreatic juice enzymes through a vagal pathway in anaesthetized rats - preliminary results

61%
Kapica M., Zabielska M., Puzio I., Jankowska A., Kato I., Kuwahara A., Zabielski R.
Journal of Physiology and Pharmacology. Supplement
|
2007
|
tom 58
|
nr 3
123-130
8
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Central and local (enteric) action of orexins

61%
Korczynski W., Ceregrzyn M., Matyjek R., Kato I., Kuwahara A., Wolinski J., Zabielski R.
Journal of Physiology and Pharmacology. Supplement
|
2006
|
tom 57
|
nr 6
17-42
Orexin-A (OXA, hyprocretin-1) and orexin-B (OXB, hypocretin-2) are peptides derived from the same 130 amino acid long precursor (prepro-orexin) that bind and activate two closely related orphan G protein-coupled receptors. Orexins and their receptors were first discovered in the rat brain, and soon after that in peripheral neural structures, including the vagal nerve and enteric nervous system, and in other structures involving the gastrointestinal tract diffuse neuroendocrine system, pancreas tissue, stomach and intestinal mucosa. Orexins and their receptors were also demonstrated in the testes, adrenals, kidneys and placenta. This review is focused on central and enteric actions. Originally, orexins were considered to be neurotransmitters that centrally stimulate food intake in animals and humans, but it soon became evident that their action is broader due to activation of a large number of neuronal pathways involved in energy homeostasis, sleep-awake behavior, nociception, reward seeking, food and drug addiction, as well as reproduction, cardiovascular and adrenal function. In the gastrointestinal tract, orexins have been found so far to affect gastrointestinal motility and gastric, intestinal and pancreatic secretions. The effects were observed following central (intraventricular) or local (intraluminal, intraarterial), but not peripheral (intravenous), administrations of orexins. Since the expression of orexins in the gastrointestinal tract is enhanced during fasting, and fasting reveals many of the orexin gastrointestinal effects, it seems probable that on the local level, orexins keep the gastrointestinal tract functions ready during fasting and play a role in brain-gut axis control.
9
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Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions

61%
Tazoe H., Otomo Y., Kaji I., Tanaka R., Karaki S.-I., Kuwahara A.
Journal of Physiology and Pharmacology. Supplement
|
2008
|
tom 59
|
nr 2
Short chain fatty acids (SCFAs) are the major anions in the large intestine. They are produced by a bacterial fermentation of dietary fiber. SCFAs are known to have a variety of physiological and pathphysiological effects on intestine. However, the mechanisms by which intraluminal SCFAs are sensed are not known. In 2003, two orphan G protein coupled receptors (GPRs), GPR41 and GPR43, have been cloned and demonstrated to be receptors for SCFAs. Thus, we had attempted to make antibodies raised against GPR43 and GPR41 to elucidate the roles of SCFAs on colonic functions. We have also evaluated the effects of SCFAs on colonic motility to define the physiological roles on luminal SCFAs. In rat and human colon, GPR43 protein was detected by Western blot analysis in extracts of whole wall and separated mucosa, but not in muscle plus submucosa extract. By immunohistochemistry, GPR43 immunoreactivity was localized with enteroendocrine cells expressing peptide YY, whereas 5-HT immunoreactive enteroendocrine cells were not immunoreactive for GPR43. GPR41 immunoreactivity was also found in human colon. In functional studies, propionate and butyrate concentration-dependently (10 µM - 10 mM) induced phasic and tonic contractions in rat colonic circular muscle. The propionate-induced phasic contraction was attenuated by atropine, tetrodotoxin and the 5-HT4 receptor antagonists SB204070. However, acetate did not induce phasic or tonic contractions. Propionate-induced responses were not observed in mucosal free preparations. The present results suggest that the SCFA-induced physiological effects on colonic functions might be attributable to the activation of SCFA receptors on epithelial cells in the colon.
10
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Pretreatment with obestatin inhibits the development of cerulein-induced pancreatitis

51%
Ceranowicz P., Warzecha Z., Dembinski A., Cieszkowski J., Dembinski M., Sendur R., Kusnierz-Cabala B., Tomaszewska R., Kuwahara A., Kato I.
Journal of Physiology and Pharmacology
|
2009
|
tom 60
|
nr 3
95-101
Obestatin is a peptide derived from the proghrelin, a common prohormone for ghrelin and obestatin. Obestatin, like the ghrelin has been originally extracted from rat stomach, and the stomach seems to be a major source of circulating obestatin. Previous studies have shown that administration of ghrelin exhibits protective effect in the pancreas, inhibiting the development of acute pancreatitis. Recent study has shown that obestatin promotes survival of ß-cells and pancreatic islets. Aim of the present study was to investigate the influence of obestatin administration on the development of cerulein-induced pancreatitis. Studies were performed on male Wistar rats. Acute pancreatitis was induced by cerulein given intraperitoneally 5 times at a dose of 50 µg/kg/dose with 1-h intervals. Obestatin was injected twice intraperitoneally at the dose of 4, 8 or 16 nmol/kg/dose. In control saline-treated rats, obestatin was without effect on pancreatic morphology, serum activity of pancreatic enzymes, serum level of pro-inflammatory interleukin-1b or pancreatic cells proliferation. In animals with induction of acute pancreatitis, morphological examination showed that administration of obestatin decreased pancreatic leukocyte infiltration and vacuolization of acinar cells. These effects were accompanied by reduction in the pancreatitis-evoked increase in serum level of pancreatic digestive enzymes, lipase amylase and poly-C ribonuclease. Obestatin administered at the highest dose of 16 nmo/kg/dose reduced serum activity of these enzymes by 33, 42 and 44%, respectively. Also serum concentration of pro-inflammatory interleukin-1ß was decreased by obestatin in rats with acute pancreatitis; whereas the pancreatitis-evoked decrease in pancreatic blood flow and pancreatic DNA synthesis was partially reversed. Administration of obestatin reduces the severity of cerulein-induced acute pancreatitis. This effect is related, at least in part, to the improvement of pancreatic blood flow and reduction in pro-inflammatory interleukin-1ß release.
11
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Role of hormonal axis, growth hormone - IGF-1, in therapeutic effect of ghrelin in the course of cerulein-induced acute pancreatitis

51%
Ceranowicz D., Warzecha Z., Debinski A., Ceranowicz P., Cieszkowski J., Kusnierz-Cabala B., Tomaszewska R., Kuwahara A., Kato I.
Journal of Physiology and Pharmacology
|
2010
|
tom 61
|
nr 5
12
Content available remote

Treatment with ghrelin accelerates the healing of acetic acid-induced gastric and duodenal ulcers in rats

51%
Ceranowicz P., Warzecha Z., Dembinski A., Sendur R., Cieszkowski J., Ceranowicz D., Pawlik W. W., Kuwahara A., Kato I., Konturek P. C.
Journal of Physiology and Pharmacology
|
2009
|
tom 60
|
nr 1
87-98
Recent studies have shown that ghrelin exhibits gastroprotective effects. The aim of present study was to examine the influence of ghrelin administration on the healing of chronic gastric and duodenal ulcers and to evaluate the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this process. In pituitary-intact or hypophysectomized rats, chronic gastric and duodenal ulcers were induced by acetic acid. After induction of ulcers, rats were treated intraperitoneally twice a day with saline, ghrelin (4, 8 or 16 nmol/kg/dose) or IGF-1 (20 nmol/kg/dose) for six or ten days. In animals with intact pituitary, treatment with ghrelin increased serum level of GH and IGF-1. These effects were accompanied by the increase in mucosal cell proliferation, mucosal blood flow and healing rate of gastric and duodenal ulcers. After hypophysectomy, the significant increase in serum level of endogenous ghrelin was observed, but the healing of gastric and duodenal ulcers was delayed. This effect was accompanied by a significant decrease in serum concentration of endogenous GH and IGF-1, and reduction in mucosal blood flow and DNA synthesis. In hypophysectomized rats, administration of exogenous ghrelin was without any effect on serum level of GH and IGF-1, healing rate of gastroduodenal ulcers or mucosal cell proliferation. In contrast to this effect, administration of IGF-1 increased mucosal cell proliferation, healing rate of gastroduodenal ulcers and mucosal blood flow in hypophysectomized rats. Conclusion: Treatment with ghrelin accelerates healing of chronic gastroduodenal ulcers and this effect is mediated by the release of endogenous GH and IGF-1.
13
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Influence of fundectomy and intraperitoneal or intragastric administration of apelin on apoptosis, mitosis, and DNA repair enzyme OGG1,2 expression in adult rats gastrointestinal tract and pancreas

51%
Antushevich H., Pawlina B., Kapica M., Krawczynska A., Herman A. P., Kuwahara A., Kato I., Zabielski R.
Journal of Physiology and Pharmacology
|
2013
|
tom 64
|
nr 4
14

The apelin-13 influences the activity of pancreatic enzymes in young rats

51%
Antushevich H., Kapica M., Kuwahara A., Kato I., Krawczynska A., Herman A. P., Pawlina P., Zabielski R.
Journal of Animal and Feed Sciences
|
2016
|
tom 25
|
nr 2
Apelin and its APJ receptor are present inter alia in colostrum and in the young animal gastrointestinal tract. This peptide exerts numerous effects participating in the appetite and drinking behaviour, gastric acid and insulin secretion. The aim of the study was to investigate the effect of apelin-13 on the activity of pancreatic and gastric enzymes in young animals. The two experiments were carried out on weaning Wistar rats (50 ± 10 g) which received the apelin-13 or physiological saline (in the corresponding control groups) by intragastric or intraperitoneal way twice a day for 10 days (100 nmol · kg–1 body weight). At the end of each experiment rats were sacrificed and blood samples were collected for apelin and cholecystokinin (CCK) radioimmunoassay. The fragments of the pancreas and stomach were weighted and frozen for the further digestive enzymes activity analysis. The intragastric and intraperitoneal administration of apelin-13 increased plasma CCK level in young rats. The intraperitoneal injection of apelin-13 stimulated pancreatic trypsin, -amylase and lipase activity, but had no effect on the activity of gastric enzymes. On the other hand, the intragastric administration of apelin-13 stimulated only the activity of pancreatic lipase and had no effect on the activity of gastric pepsin and rennet. So, circulating apelin exerts the most pronounced effect on pancreatic enzymes activity in young rats, but neither circulating nor luminal apelin influences gastric enzymes activity. Regardless the route of administration, apelin stimulates lipase activity which points out its considerable role in the regulation of the fat digestion.
15
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Therapeutic effect of ghrelin in the course of cerulein-induced acute pancreatitis in rats

51%
Warzecha Z., Ceranowicz P., Dembinski A., Cieszkowski J., Kusnierz-Cabala B., Tomaszewska R., Kuwahara A., Kato I.
Journal of Physiology and Pharmacology
|
2010
|
tom 61
|
nr 4
419-427
Recent studies have shown that pretreatment with ghrelin exhibits protective effect in the gut. Administration of ghrelin reduces gastric mucosal damage, as well as inhibits the development of experimental pancreatitis. However, this protective effect requires administration of ghrelin before gastric or pancreatic damage and thus has a limited clinical value. The aim of present study was to assess the influence of ghrelin administered after development of acute pancreatitis on the course of this disease. Acute pancreatitis was induced by cerulein. Ghrelin was administered twice a day for 1, 2, 4, 6 or 9 days at the dose of 4, 8 or 16 nmol/kg/dose. The first dose of ghrelin was given 24 hours after last injection of cerulein. The severity of acute pancreatitis was assessed between 0 h and 10 days after cessation of cerulein administration. Administration of caerulein led to the development of acute edematous pancreatitis and maximal severity of this disease was observed 24 hours after induction of pancreatitis. Treatment with ghrelin reduced morphological signs of pancreatic damage such as pancreatic edema, leukocyte infiltration and vacuolization of acinar cells, and led to earlier regeneration of the pancreas. Also biochemical indexes of the severity of acute pancreatitis, serum activity of lipase and amylase were significantly reduced in animals treated with ghrelin. These effects were accompanied by an increase in the pancreatic DNA synthesis and a decrease in serum level of pro-inflammatory interleukin-1ß. Administration of ghrelin improved pancreatic blood flow in rats with acute pancreatitis. We conclude that: (1) treatment with ghrelin exhibits therapeutic effect in caerulein-induced experimental acute pancreatitis; (2) this effect is related, at least in part, to the improvement of pancreatic blood flow, reduction in proinflammatory interleukin-1b and stimulation of pancreatic cell proliferation.
16
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Variable effect of ghrelin administration on pancreatic development in young rats. Role of insulin-like growth factor-1

51%
Dembinski A., Warzecha Z., Ceranowicz P., Bielanski W., Cieszkowski J., Dembinski M., Pawlik W. W., Kuwahara A., Kato I., Konturek P. C.
Journal of Physiology and Pharmacology
|
2005
|
tom 56
|
nr 4
Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been primarily isolated from the human and rat stomach. Ghrelin has been shown to stimulate appetite and fat deposition in adult rats and humans. The aim of this study was to investigate the effect of ghrelin administration on pancreatic growth in suckling, weaned and peripubertal seven week old rats. Rats were treated with saline or ghrelin (4, 8 or 16 nmol/kg/dose) intraperitoneally twice a day: suckling rats were treated for 7 or 14 days starting from the first postnatal day, three week old weaned rats and seven weeks old rats were treated for 5 days. Treatment with ghrelin did not affect animal weight in suckling or weaned rats, whereas in young seven week old rats, ghrelin caused a significant increase in body weight. Ghrelin decreased food intake in weaned rats; whereas in seven week old rats, food intake was enhanced. In suckling rats, ghrelin decreased the pancreatic weight, pancreatic amylase content, DNA synthesis and DNA content. In contrast, ghrelin increased pancreatic weight, DNA synthesis, DNA content and amylase content in weaned or young seven week old rats. Pancreatic blood flow was not affected by ghrelin in any group of rats tested. Ghrelin increased serum level of growth hormone in all rats. This effect was weak in suckling rats, higher in weaned and the highest in seven week old animals. Ghrelin did not affect serum level of insulin-like growth factor-1 (IGF-1) in suckling rats. In weaned and in seven week old rats, treatment with ghrelin caused increase in serum level of IGF-1. We conclude that ghrelin reduces pancreatic growth in suckling rats; whereas in weaned and young seven week old animals, treatment with ghrelin increases pancreatic growth. This biphasic effect of ghrelin in young animals on pancreatic growth seems to be related to age-dependent changes of the release of anabolic IGF-1.
17
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Role of leptin, ghrelin, angiotensin II and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism

42%
Zwirska-Korczala K., Adamczyk-Sowa M., Sowa P., Pilc K., Suchanek R., Pierzchala K., Namyslowski G., Misiolek M., Sadowski K., Kato I., Kuwahara A., Zabielski R.
Journal of Physiology and Pharmacology. Supplement
|
2007
|
tom 58
|
nr 1
53-64
18
Content available remote

Influence of ghrelin on gastric and duodenal growth and expression of digestive enzymes in young mature rats

42%
Warzecha Z., Dembinski A., Ceranowicz P., Dembinski M., Cieszkowski J., Konturek S. J., Polus A., Pawlik W. W., Kuwahara A., Kato I., Konturek P. C.
Journal of Physiology and Pharmacology
|
2006
|
tom 57
|
nr 3
Ghrelin, a nature ligand for the growth hormone secretagogue receptor (GHS-R), stimulates a release of growth hormone, prolactin and adrenocorticotropic hormone. Also, ghrelin increases food intake in adult rats and humans and exhibits gastroprotective effect against experimental ulcers induced by ethanol or stress. The aim of present study was to examine the influence of ghrelin administration on gastric and duodenal growth and expression of pepsin and enterokinase in young mature rats with intact or removed pituitary. Methods: Two week after sham operation or hypophysectomy, eight week old Wistar male rats were treated with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose) i.p. twice a day for 4 days. Expression of pepsin in the stomach and enterokinase in the duodenum was evaluated by real-time PCR. Results: In animals with intact pituitary, treatment with ghrelin increased food intake, body weight gain and serum level of growth hormone and insulin-like growth factor-1 (IGF-1). These effects were accompanied with stimulation of gastric and duodenal growth. It was recognized as the significant increase in gastric and duodenal weight and mucosal DNA synthesis. In both organs, ghrelin administered at the dose of 8 nmol/kg caused maximal growth-promoting effect. In contrast to these growth-promoting effects, administration of ghrelin reduced expression of mRNA for pepsin in the stomach and was without effect on expression of mRNA for enterokinase in the duodenum. Hypophysectomy alone lowered serum concentration of growth hormone under the detection limit and reduced serum level of IGF-1 by 90%. These effects were associated with reduction in daily food intake, body weight gain and gastroduodenal growth. In hypophysectomized rats, administration of ghrelin was without significant effect on food intake, body weight gain or growth of gastroduodenal mucosa. Also, serum concentration of growth hormone or IGF-1 was not affected by ghrelin administration in rats with removed pituitary. Conclusion: Administration of ghrelin stimulates gastric and duodenal growth in young mature rats with intact pituitary, but inhibits expression of mRNA for pepsin in the stomach. Growth hormone and insulin-like growth factor-1 play an essential role in growth-promoting effects of ghrelin in the stomach and duodenum.
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