MUCOSAL PROTECTIVE ACTIVITY OF PROSTAGLANDIN ANALOGS IN RODENT COLONIC INFLAMMATION

被引:15
作者
FRETLAND, DJ
WIDOMSKI, DL
ANGLIN, CP
WALSH, RE
LEVIN, S
GASIECKI, AF
COLLINS, PW
机构
[1] SEARLE RES & DEV,DEPT CHEM,SKOKIE,IL 60077
[2] SEARLE RES & DEV,DEPT PATHOL,SKOKIE,IL 60077
关键词
D O I
10.1007/BF00919345
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The mucosal protective prostaglandin analogs misoprostol, enisoprost, and SC-46275 (the 17E-18-cyclopentenyl analog of enisoprost) were tested in mouse and rat colitis induced by the intrarectal instillation of dilute acetic acid. Colitis was assessed by histology and colonic levels of myeloperoxidase (a neutrophil marker enzyme). When given as enemas 30 min ahead of colitis induction, 15(R)-15-methyl-PGE2 (arbaprostil) and 15(S)-15-methyl-PGE1 were inactive; however, misoprostol, enisoprost, and SC-46275 protected against colonic inflammation with ED50 values of 24, 12 and 1.3 mug/kg, respectively, in rats and 11, 5, and 1 mug/kg, respectively, in mice. These compounds may have utility in the medical management of human inflammatory bowel disease.
引用
收藏
页码:623 / 629
页数:7
相关论文
共 19 条
[1]   TREATMENT WITH 16,16'-DIMETHYL PROSTAGLANDIN-E2 BEFORE AND AFTER INDUCTION OF COLITIS WITH TRINITROBENZENESULFONIC ACID IN RATS DECREASES INFLAMMATION [J].
ALLGAYER, H ;
DESCHRYVER, K ;
STENSON, WF .
GASTROENTEROLOGY, 1989, 96 (05) :1290-1300
[2]   RELATIONSHIP BETWEEN ARACHIDONIC-ACID METABOLISM, MYELOPEROXIDASE ACTIVITY AND LEUKOCYTE INFILTRATION IN A RAT MODEL OF INFLAMMATORY BOWEL-DISEASE [J].
BOUGHTONSMITH, NK ;
WALLACE, JL ;
WHITTLE, BJR .
AGENTS AND ACTIONS, 1988, 25 (1-2) :115-123
[3]   CHEMISTRY AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF C-17 UNSATURATED 18-CYCLOALKYL AND CYCLOALKENYL ANALOGS OF ENISOPROST - IDENTIFICATION OF A PROMISING NEW ANTIULCER PROSTAGLANDIN [J].
COLLINS, PW ;
GASIECKI, AF ;
PERKINS, WE ;
GULLIKSON, GW ;
BIANCHI, RG ;
KRAMER, SW ;
NG, JS ;
YONAN, EE ;
SWENTON, L ;
JONES, PH ;
BAUER, RF .
JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (10) :2784-2793
[5]  
COLLINS PW, 1990, MED RES REV, V10, P419
[6]   MISOPROSTOL PROVIDES A COLONIC MUCOSAL PROTECTIVE EFFECT DURING ACETIC-ACID INDUCED COLITIS IN RATS [J].
FEDORAK, RN ;
EMPEY, LR ;
MACARTHUR, C ;
JEWELL, LD .
GASTROENTEROLOGY, 1990, 98 (03) :615-625
[7]   THE EFFECT OF LEUKOTRIENE-B4 RECEPTOR ANTAGONIST, SC-41930, ON ACETIC ACID-INDUCED COLONIC INFLAMMATION [J].
FRETLAND, DJ ;
LEVIN, S ;
TSAI, BS ;
DJURIC, SW ;
WIDOMSKI, DL ;
ZEMAITIS, JM ;
SHONE, RL ;
BAUER, RF .
AGENTS AND ACTIONS, 1989, 27 (3-4) :395-397
[8]   PROSTANOIDS CYTOPROTECTION FOR MAINTAINING REMISSION IN ULCERATIVE-COLITIS - FAILURE OF 15(R), 15-METHYLPROSTAGLANDIN-E2 [J].
GOLDIN, E ;
RACHMILEWITZ, D .
DIGESTIVE DISEASES AND SCIENCES, 1983, 28 (09) :807-811
[9]  
KEITH RH, 1985, FED PROC, V44, P1545
[10]  
KRAWISZ JE, 1984, GASTROENTEROLOGY, V87, P1344