Enhanced bradykinin-stimulated prostaglandin release in the acutely inflamed guinea pig gallbladder is due to new synthesis of cyclooxygenase 1 and prostacyclin synthase

被引:22
作者
Bogar, LJ [1 ]
Bartula, LL [1 ]
Parkman, HP [1 ]
Myers, SI [1 ]
机构
[1] Temple Univ, Sch Med, Dept Surg, Philadelphia, PA 19122 USA
关键词
prostaglandins; gallbladder; inflammation; cyclooxygenase; prostacyclin synthase;
D O I
10.1006/jsre.1999.5612
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Our previous studies have shown that acute gallbladder (GB) inflammation increases endogenous bradykinin (BK)-stimulated prostaglandin (PG) release and inhibits guinea pig (GP) GB contractility. This study examines the hypothesis that exaggerated PG release following BK stimulation in the inflamed guinea pig GB is due to new protein synthesis of cyclooxygenase 1 (COX-1) and prostacyclin synthase (PS). Materials and methods. Male Hartley GPs (450-550 g) were anesthetized and underwent common bile duct ligation (BDL, a model of acute inflammation). GBs were harvested after 3 days from BDL and control groups. Tissue slices were prepared and placed in oxygenated tissue culture medium at 37 degrees C far 1 h (basal) and for a second hour in medium alone (carrier, Car), medium plus 10(-6) M BK, or medium plus 10-6 RI BK plus cycloheximide 100 mu g/ml (BK + CX). The medium was assayed for net release of 6-keto-PGF(1 alpha) (PGI(2) metabolite), thromboxane B-2 (TxB(2)), PGE(2), leukotriene B-4 (LTB4), and C-4 (LTC4) by enzyme immunoassay and data are reported as nanograms per milligram of protein. GB tissue from control and BDL groups was examined for COX-1, COX-2, PS, and inducible nitric oxide synthase (iNOS) content by Western blot analysis, analyzed by densitometry, and reported as densitometry units. Results. All data were analyzed by ANOVA and t test and reported as means +/- SEM, N greater than or equal to 5. BK increased the release of PGI, and PGE, from the control group and markedly exaggerated release of PG;I, and PGE2 from the BDL GP gallbladder. This exaggerated PGI, and PGE, release was greatly diminished by inhibition of new protein synthesis with cycloheximide. TxB(2), LTB4, and LTC4 showed no significant differences between any groups. COX-1 and PS contents were significantly elevated in the BDL group compared with control. COX-2 and iNOS were not present in control or BDL GBs. Conclusions. These data suggest that the enhanced BK-stimulated PG release seen in the acutely inflamed GP gallbladder is due to the synthesis of new COX-1 and PS enzymes. (C) 1999 Academic Press.
引用
收藏
页码:71 / 76
页数:6
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