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  • 1
    Digitale Medien
    Digitale Medien
    Effects of the bradykinin antagonist, icatibant (Hoe 140), on pancreas and liver functions during and after caerulein-induced pancreatitis in rats (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 557-564 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Key words Bradykinin antagonists ; Icatibant(Hoe 140) ; Pancreatitis (experimental) ; Caerulein
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  It has been found earlier that the bradykinin antagonist, icatibant (Hoe 140), prevents the pancreatic oedema and the ensuing hypotension and haemoconcentration, and facilitates the removal of activated enzymes from the tissue during caerulein-induced acute pancreatitis. For a potential therapeutic use of the compound in clinical situations it is essential to investigate whether the associated increase in enzyme activities in the blood serum has any adverse effects on the pancreas itself or on other organs. Normal amylase secretion into the biliopancreatic duct stimulated by a low dose of caerulein (0.4 nmol kg-1 h-1, i.v.) was not affected by icatibant (100 nmolkg-1, s.c.). Acute pancreatitis, induced by a high dose of caerulein (4 nmol kg-1 h-1 for 2 h, i.v.), resulted in elevations in the activities of amylase and lipase in the pancreatic tissue and in the blood serum lasting for at least 4 h after the end of the caerulein infusion. While the rise in enzyme activities in the blood serum was augmented in icatibant-treated rats only at the end of the caerulein-infusion, the enzyme accumulation in the pancreas was significantly reduced by icatibant for at least 4 h after the end of the caerulein infusion. The secretion of amylase and lipase into the biliopancreatic duct was significantly increased only during the first 20 min of acute pancreatitis; in rats pre-treated with icatibant, no significant increase could be observed. Twenty-four hours after induction of pancreatitis, a low-dose caerulein stimulation of the exocrine function of the pancreas led to a reduced but sustained secretion of amylase regardless of whether the animals had received icatibant or not. During the first 45 min of pancreatitis, blood glucose concentrations were significantly reduced, but returned to values not different from those obtained in saline-infused controls. This effect was not affected by icatibant. No changes in the response to an i.v. glucose tolerance test were found on the day after induction of acute pancreatitis. The serum activities of glutamic pyruvic transaminase and γ-glutamyl transpeptidase determined up to 24 h after induction of pancreatitis were not different from saline controls. Icatibant had no effect on the activities of these enzymes. It is concluded that during caerulein-induced acute pancreatitis normal exocrine secretion of pancreatic enzymes into the pancreatic duct ceases almost immediately. Pre-treatment with icatibant significantly reduces the accumulation of activated enzymes in the pancreatic tissue for several hours after induction of pancreatitis while a concomitant augmentation in enzyme activities in the blood serum lasts much shorter. There is no indication of adverse effects on the function of the endocrine or exocrine pancreas and that of the liver, either during the acute stages of pancreatitis or during the recovery period.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00169391
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Effects of the bradykinin antagonist, icatibant (Hoe 140), on pancreas and liver functions during and after caerulein-induced pancreatitis in rats (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 557-564 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Bradykinin antagonists ; Icatibant (Hoe 140) ; Pancreatitis (experimental) ; Caerulein
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract It has been found earlier that the bradykinin antagonist, icatibant (Hoe 140), prevents the pancreatic oedema and the ensuing hypotension and haemoconcentration, and facilitates the removal of activated enzymes from the tissue during caerulein-induced acute pancreatitis. For a potential therapeutic use of the compound in clinical situations it is essential to investigate whether the associated increase in enzyme activities in the blood serum has any adverse effects on the pancreas itself or on other organs. Normal amylase secretion into the biliopancreatic duct stimulated by a low dose of caerulein (0.4 nmol kg−1 h−1, i.v.) was not affected by icatibant (100 nmolkg−1, s.c.). Acute pancreatitis, induced by a high dose of caerulein (4 nmol kg−1 h−1 for 2 h, i.v.), resulted in elevations in the activities of amylase and lipase in the pancreatic tissue and in the blood serum lasting for at least 4 h after the end of the caerulein infusion. While the rise in enzyme activities in the blood serum was augmented in icatibant-treated rats only at the end of the caerulein-infusion, the enzyme accumulation in the pancreas was significantly reduced by icatibant for at least 4 h after the end of the caerulein infusion. The secretion of amylase and lipase into the biliopancreatic duct was significantly increased only during the first 20 min of acute pancreatitis; in rats pre-treated with icatibant, no significant increase could be observed. Twenty-four hours after induction of pancreatitis, a low-dose caerulein stimulation of the exocrine function of the pancreas led to a reduced but sustained secretion of amylase regardless of whether the animals had received icatibant or not. During the first 45 min of pancreatitis, blood glucose concentrations were significantly reduced, but returned to values not different from those obtained in saline-infused controls. This effect was not affected by icatibant. No changes in the response to an i.v. glucose tolerance test were found on the day after induction of acute pancreatitis. The serum activities of glutamic pyruvic transaminase and γ-glutamyl transpeptidase determined up to 24 h after induction of pancreatitis were not different from saline controls. Icatibant had no effect on the activities of these enzymes. It is concluded that during caerulein-induced acute pancreatitis normal exocrine secretion of pancreatic enzymes into the pancreatic duct ceases almost immediately. Pre-treatment with icatibant significantly reduces the accumulation of activated enzymes in the pancreatic tissue for several hours after induction of pancreatitis while a concomitant augmentation in enzyme activities in the blood serum lasts much shorter. There is no indication of adverse effects on the function of the endocrine or exocrine pancreas and that of the liver, either during the acute stages of pancreatitis or during the recovery period.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00169391
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 3
    Digitale Medien
    Digitale Medien
    Caerulein, substance P, serotonin, and cholinomimetics induce rhythmic contractions of the intestinal circular muscle (1980)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 312 (1980), S. 131-137 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Guinea-pig ileum ; Intestinal circular muscle ; Caerulein ; Substance P ; 5-Hydroxytryptamine ; Cholinomimetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. The mechanical activity of the circular muscle of the isolated guinea-pig ileum in response to various spasmogenic compounds was investigated. Contractions were recorded isotonically. 2. Caerulein (〉0.1 nM), bombesin (〉1 nM), substanceP (〉2 nM), 5-hydroxytryptamine and bethanechol (〉0.5 μM), and dimethylphenylpiperazinium (〉3 μM) induced rhythmic contractions superimposed on an increased tone. 3. Tetrodotoxin (0.93 μM) abolished the actions of caerulein, bombesin, 5-hydroxytryptamine, and dimethylphenylpiperazinium, partially inhibited the effect of substance P, but did not influence the contractile response to bethanechol. 4. The met-enkephalin analogue FK 33-824 (0.17 μM) abolished the action of only those compounds whose action was suppressed by tetrodotoxin, whereas noradrenaline (1.78 μM) blocked the effect of all six spasmogenic compounds studied. 5. An indirect action of caerulein, bombesin, substance P, 5-hydroxytryptamine, or dimethylphenylpiperazinium on the circular muscle by excitation of cholinergic neurones could be excluded because of the ineffectivity of tropicamide (3.64 μM). 6. Experiments employing tachyphylaxis to either substance P or 5-hydroxytryptamine showed that the contractile response to caerulein may involve release of endogenous substance P and that the action of substance P may be mediated via an indoleaminergic pathway. 7. The results imply that excitatory neurotransmitter candidates of the intestine such as cholecystokinin-like peptides (an analogue of which is caerulein), bombesin-like peptides, substance P, 5-hydroxytryptamine, and acetylcholine are able to induce rhythmic, peristalsis-like contractions of the intestinal circular muscle in physiologically relevant concentrations.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00569721
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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    Artikel (Nationallizenzen)
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