Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of ketanserin, a S 2 (5-hydroxytryptamine 2; 5-HT 2)-serotonergic receptor antagonist, on cerulein-induced pancreatitis in the rat. Large pharmacological doses of cerulein induced acute pancreatitis in the rat. Ketanserin reduced the cerulein-induced increase in serum amylase concentration in a dose-dependent manner. Treatment with 10 mg/kg of ketanserin per os markedly improved cerulein-induced pancreatitis and was associated with a significant reduction of the increase in serum amylase concentration. In addition, a very specific serotonin S 2 antagonist, ritanserin which has no antihypertensive effect, also reduced the cerulein-induced increase in the serum amylase concentration. These results suggest that S 2 (5-HT 2) may play a role in pathophysiology of cerulein-induced pancreatitis in the rat.
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PMID:Effects of the S2-serotonergic receptor antagonist, ketanserin, on cerulein-induced pancreatitis in the rat. 137 Nov 80

The effects of R-102444 ((2R, 4R)-4-lauroyloxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy]ethyl-1-methylpyrrolidine hydrochloride) and its active metabolite R-96544 ((2R, 4R)-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy]ethyl-4-hydroxy-1-methylpyrrolidine hydrochloride), potent and selective 5-hydroxytryptamine 2A (5-HT2A) receptor antagonists, on development of pancreatitis were investigated in experimental models of acute and chronic pancreatitis. Rat acute pancreatitis was induced by caerulein (20 microg/kg) intraperitoneal injection and by pancreatic duct ligation. In both the models, serum amylase and lipase activities were markedly increased. R-102444 dose-dependently reduced these enzyme activities at a dose range of 10 to 100 mg/kg (p.o.) for the caerulein model and 0.3 to 10 mg/kg (p.o.) for the ligation model. In a mouse model of acute pancreatitis induced by a choline-deficient, ethionine (0.5%)-supplemented diet, subcutaneous administration of R-96544 (10-100 mg/kg, bid) reduced serum amylase activity. Histological analysis showed that R-96544 dose-dependently attenuated pancreatic necrosis, inflammation and vacuolization. The effect of R-102444 was further examined in male Wistar Bonn/Kobori rats (4-9 months of age) which spontaneously show pancreatic fibrosis and parenchymal destruction compatible with human chronic pancreatitis. In Wistar Bonn/Kobori rats (from 3 to 9 months of age) fed a diet containing 0.017% and 0.17% of R-102444, pancreatic weight, pancreatic protein and amylase content were higher compared to those in non-treated pancreatitis control rats. Histological analysis showed that R-102444 suppressed parenchymal destruction and replacement with adipose tissue, indicating inhibition of pancreatic atrophy. These results clearly indicate that R-102444 and R-96544 inhibit the progression of acute and chronic pancreatitis and support the contention of possible involvement of 5-HT2A receptors in the progression of experimental pancreatitis.
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PMID:Effects of R-102444 and its active metabolite R-96544, selective 5-HT2A receptor antagonists, on experimental acute and chronic pancreatitis: Additional evidence for possible involvement of 5-HT2A receptors in the development of experimental pancreatitis. 1618 55

Acute pancreatitis remains a potentially life-threatening disease associated with gastrointestinal motility disturbances. Prokinetic agents may be useful to overcome these motility disturbances. In this study, we investigated the effect of acute necrotizing pancreatitis (ANP) on gastrointestinal motility in female mice and evaluated the effect of tegaserod, a prokinetic 5-hydroxytryptamine-4 (5HT4) receptor agonist. ANP was induced by feeding mice a choline-deficient ethionine-supplemented diet during 72 h. In vivo intestinal motility was measured as the geometric centre (GC) of 25 glass beads 30-120-360 min after gavage. Colonic peristaltic activity was studied using a modified Trendelenburg set-up. ANP significantly decreased GC 30-120-360 min after bead gavage, associated with a significant increase of myeloperoxidase in the proximal small intestine and colon, but not in the stomach or distal small intestine. Tegaserod significantly ameliorated GC 360 min after bead gavage in control and pancreatitis mice. In isolated colonic segments, ANP significantly decreased the amplitude of peristaltic waves and increased the interval between peristaltic contractions. Tegaserod normalized the disturbed interval. In conclusion, ANP impairs gastric, small intestinal and colonic motility in mice. Tegaserod improves ANP-induced motility disturbances in vivo and in vitro, suggesting a therapeutic benefit of prokinetic 5HT4 receptor agonists in the treatment of pancreatitis-induced ileus.
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PMID:Experimental pancreatitis disturbs gastrointestinal and colonic motility in mice: effect of the prokinetic agent tegaserod. 1788 37

In a previous article, we showed that a potent serotonin-, 5-hydroxytryptamine-2A (5-HT(2A)) antagonist, risperidone, ameliorated cerulein-induced edematous pancreatitis in mice. In the present article, young female mice were fed a choline-deficient, ethionine-supplemented diet. All of the mice developed severe necrotic pancreatitis, and approximately 50% of them died within 4 days. Serum levels of proinflammatory interleukin (IL)-6 significantly increased on day 3 and returned toward the control on day 4 of choline-deficient ethionine-supplemented (CDE) diet treatment. The time course of IL-6 levels paralleled those of plasma amylase and lipase activities. On the other hand, platelet counts significantly decreased on day 3, and the change became more marked on day 4, coinciding with mortality and histological alterations of the pancreas (edema, inflammatory cell infiltration, necrosis). Preceding these changes, plasma levels of 5-hydroxyindoleacetic acid (5-HIAA) increased on feeding a CDE diet to reach a peak on day 3 and returned toward the control on day 4. Risperidone (0.1-3.2 mg/kg twice a day) hardly affected the 5-HIAA levels but dose-dependently attenuated the serum IL-6 levels, plasma amylase/lipase levels, platelet counts, histological alterations, and mortality of diet-induced pancreatitis mice. These results are discussed in relation to the pathogenesis of acute pancreatitis. Thus, we speculate that acinar cell injury triggers local inflammatory reactions and, if coincided with enhanced IL-6 release, leads to a systemic inflammatory response syndrome, which is responsible for the mortality. In addition, it is suggested that diet-induced 5-HT release and 5-HT(2A) receptor activation are involved in this whole process of pancreatitis development. Risperidone may provide a new therapy for the disease.
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PMID:Risperidone attenuates local and systemic inflammatory responses to ameliorate diet-induced severe necrotic pancreatitis in mice: it may provide a new therapy for acute pancreatitis. 1883 8