白细胞介素1β抑制大鼠胃排空：通过前列腺素和促肾上腺皮质激素释放因子介导。

Interleukin 1 beta inhibits gastric emptying in rats: mediation through prostaglandin and corticotropin-releasing factor.

作者信息

Sütö G, Király A, Taché Y

机构信息

Center for Ulcer Research, Veterans Administration Wadsworth Medical Center, Los Angeles, California.

出版信息

Gastroenterology. 1994 Jun;106(6):1568-75. doi: 10.1016/0016-5085(94)90412-x.

DOI:10.1016/0016-5085(94)90412-x

PMID:8194703

Abstract

BACKGROUND/AIMS: Interleukin 1 beta (IL-1 beta) increases the release of corticotropin-releasing factor (CRF) in the brain through prostaglandin pathways. Because central CRF inhibits gastric motor function, the influence and mechanism of action of intracisternal injection of IL-1 beta on gastric emptying were investigated.

METHODS

The 20-minute rate of gastric emptying of a nonnutrient test meal was assessed by the phenol red methylcellulose method 30 minutes after injection of human recombinant IL-1 beta in conscious rats.

RESULTS

IL-1 beta injected intracisternally (0.01-1 ng) or intravenously (0.01-10 ng) dose-dependently decreased gastric emptying by 10%-82% and 0%-89%, respectively. The median effective dose (ED50) was 30-fold lower when IL-1 beta was injected intracisternally (0.1 ng) than intravenously (3 ng). The inhibitory effect of intracisternal IL-1 beta had a rapid onset (within 20 minutes) and was long-lasting (6 hours). Indomethacin (5 mg/kg, intraperitoneally) completely prevented the 61% inhibition induced by intracisternal IL-1 beta (0.1 ng) but had no effect on CRF-induced (600 ng) 72% inhibition of gastric emptying. The intracisternal injection of the IL-1 receptor antagonist (100 ng) or the CRF antagonist [DPhe12, [DPhe12,Nle21,38,C alpha MeLeu37]CRF12-41 (20 micrograms) prevented by 100% and 52%, respectively, the inhibition of gastric emptying evoked by intracisternal IL-1 beta (0.1 ng). The antagonists alone had no effect on basal gastric emptying.

CONCLUSIONS

IL-1 beta acts in the brain to induce a long-lasting inhibition of gastric emptying; IL-1 beta action is mediated through central IL-1 receptors and prostaglandin- and CRF-dependent mechanisms.

摘要

背景/目的：白细胞介素1β（IL-1β）通过前列腺素途径增加大脑中促肾上腺皮质激素释放因子（CRF）的释放。由于中枢CRF抑制胃运动功能，因此研究了脑池内注射IL-1β对胃排空的影响及其作用机制。

方法

在清醒大鼠中注射人重组IL-1β 30分钟后，采用酚红甲基纤维素法评估非营养性试验餐20分钟的胃排空率。

结果

脑池内注射（0.01 - 1 ng）或静脉注射（0.01 - 10 ng）IL-1β分别以剂量依赖方式使胃排空减少10% - 82%和0% - 89%。脑池内注射IL-1β（0.1 ng）时的半数有效剂量（ED50）比静脉注射（3 ng）低30倍。脑池内IL-1β的抑制作用起效迅速（20分钟内）且持续时间长（6小时）。吲哚美辛（5 mg/kg，腹腔注射）完全阻止了脑池内IL-1β（0.1 ng）诱导的61%的抑制作用，但对CRF诱导的（600 ng）胃排空72%的抑制作用无影响。脑池内注射IL-1受体拮抗剂（100 ng）或CRF拮抗剂[DPhe12，[DPhe12，Nle21，38，CαMeLeu37]CRF12 - 41（20 μg）分别100%和52%地阻止了脑池内IL-1β（0.1 ng）引起的胃排空抑制。单独使用拮抗剂对基础胃排空无影响。