@article {Yoshino1495, author = {Takako Yoshino and Isamu Yamaguchi}, title = {Possible Involvement of 5-HT2 Receptor Activation in Aggravation of Diet-Induced Acute Pancreatitis in Mice}, volume = {283}, number = {3}, pages = {1495--1502}, year = {1997}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Acute pancreatitis was induced in mice by feeding with a choline-deficient ethionine-supplemented diet. All the mice developed acute pancreatitis, and approximately 80\% of them died within 4 days. Stereomicroscopic and light microscopic examinations revealed that pancreatic necrosis and circulatory disturbance that were not apparent on day 1 were increased markedly on days 2 and 3. Serum levels of pancreatic enzymes were normal or reduced on day 1 but then increased to peak on day 3. Plasma 5-hydroxyindoleacetic acid levels, which may indicate serotonin release, were significantly increased on days 1 through 3. Pretreatment with d,l-p-chlorophenylalanine methylester hydrochloride (200{\textendash}400 mg/kg) significantly attenuated the mortality of the mice with pancreatitis. Dose-dependent attenuation was also obtained with ketaserin (0.01{\textendash}10 mg/kg), cyproheptadine (0.01{\textendash}10 mg/kg), pindolol (0.1{\textendash}100 mg/kg) and NAN-190 (0.1{\textendash}100 mg/kg), but not with 0.01 to 10 mg/kg of ICS205-930 or M-840, and the activities were significantly correlated with the binding affinities for serotonin2 receptor on the rat cerebral cortex. In addition, ketanserin or cyproheptadine attenuated the morphologic changes in the choline-deficient ethionine-supplemented diet mice at a dose (3.2 mg/kg) that hardly affected the serum enzyme levels. We propose that serotonin2 receptor activation plays an important role in the aggravation of diet-induced acute pancreatitis. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/283/3/1495}, eprint = {https://jpet.aspetjournals.org/content/283/3/1495.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }