INTERLEUKIN-1-BETA-INDUCED AND TUMOR-NECROSIS-FACTOR-INDUCED INHIBITION OF RAT GASTRIC FUNDUS MOTILITY IN-VITRO
INTERLEUKIN-1-BETA-INDUCED AND TUMOR-NECROSIS-FACTOR-INDUCED INHIBITION OF RAT GASTRIC FUNDUS MOTILITY IN-VITRO
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DOI：
10.1016/1043-6618(94)80084-7
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发表时间：
1994-07-01
影响因子：
9.3
通讯作者：
NAVARRA, P
中科院分区：
文献类型：
--
作者：
MONTUSCHI, P;TRINGALI, G;NAVARRA, P
In this study, we compared the effects of interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) on in vitro rat gastric fundus motility. IL-1 beta and TNF produced rapid, concentration-dependent relaxation of the rat gastric fundus strips with maximal effect at 300 pg ml(-1) and 10 ng ml(-1), and estimated EC(50)s at 10 and 450 pg ml(-1), respectively.The relaxant effects of IL-1 beta and TNF were not influenced by the inhibition of cyclo-oxygenase or NO-synthase activities. IL-1 beta- and TNF-induced gastric relaxations were inhibited by BW 755c, which inhibits both cyclo-oxygenase and lipoxygenase (LO), BW A4c, which selectively inhibits the 5-LO pathway, and SC 41930, a selective leukotriene B4 (LTB4) receptor antagonist, providing pharmacological evidence that LTB4 is involved in the relaxant effects of both cytokines.The IL-1 beta- and TNF-induced activation of 5-LO pathway did not appear to be triggered by phospholipase A2. An alternative pathway could involve the activation of a phospholipase C, specific for phosphatidylcholine, from which, in sequence: the formation of diacylglycerol (DAG), DAG-induced activation of protein kinase C and the formation of free arachidonic acid from DAG would ensue. This mechanism is suggested by the finding that LTB4 is able to mimic cytokine-induced strip relaxation only in the presence of phorbol 12-myristate 13-acetate, which selectively activates protein kinase C.
