抗炎药对表皮生长因子-尿抑胃素诱导的豚鼠胃离体纵行平滑肌条收缩的抑制作用。

Inhibition by anti-inflammatory agents of contraction induced by epidermal growth factor-urogastrone in isolated longitudinal smooth muscle strips from guinea-pig stomach.

作者信息

Itoh H, Muramatsu I, Patel P, Lederis K, Hollenberg M D

机构信息

Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Alberta, Canada.

出版信息

Br J Pharmacol. 1988 Nov;95(3):821-9. doi: 10.1111/j.1476-5381.1988.tb11710.x.

DOI:10.1111/j.1476-5381.1988.tb11710.x

PMID:3264733

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1854213/

Abstract

Epidermal growth factor-urogastrone (EGF-URO) caused a concentration-dependent contractile response of longitudinal muscle strips from the gastric body of the guinea-pig stomach. The contractile response to EGF-URO was monophasic, with tension returning rapidly to baseline. Desensitization was evident in that further addition of EGF-URO to the organ bath did not cause a second contraction. 2. Preincubation with indomethacin, ibuprofen, naproxen and aspirin markedly inhibited the contractions induced by EGF-URO with an order of potency (indomethacin greater than naproxen greater than ibuprofen greater than aspirin) that reflected the ability of these agents to inhibit cyclo-oxygenase. 3. The data indicate that prostanoids mediate the action of EGF-URO in the longitudinal muscle preparation. 4. Auranofin (0.5 to 50 microM), a chrysotherapeutic agent with antiproliferative properties used for treating rheumatoid arthritis, also markedly inhibited the EGF-URO response; however, other gold-containing compounds (aurothioglucose or gold sodium thiomalate at 30 to 100 microM) failed to cause significant inhibition. 5. Preincubation of preparations for 2 h with 1 microM hydrocortisone, prednisolone or dexamethasone caused an inhibition of EGF-URO-induced contraction of approximately 50%. However, steroids lacking either a 17 alpha-hydroxyl (corticosterone) or an 11 beta-hydroxyl (cortisone, deoxycorticosterone, prednisone) substituent did not inhibit the contraction caused by EGF-URO. For hydrocortisone, the inhibitory effect was half-maximal at 0.2 microM and was maximal at 1 microM. Cycloheximide (10 microM) blocked the inhibitory action of hydrocortisone and potentiated the contractile action of EGF-URO. 6. The ability of a variety of steroidal and non-steroidal anti-inflammatory agents to interfere with the action of EGF-URO in a smooth muscle preparation suggests that these agents may also inhibit the action of EGF-URO mediated by prostanoids in other target tissues. 7. The data also point to a potential role for EGF-URO in regulating gastric motility.

摘要

表皮生长因子-尿抑胃素（EGF-URO）可引起豚鼠胃体纵行肌条浓度依赖性收缩反应。对EGF-URO的收缩反应呈单相性，张力迅速恢复至基线水平。脱敏现象明显，因为向器官浴槽中进一步添加EGF-URO不会引起第二次收缩。2. 用吲哚美辛、布洛芬、萘普生和阿司匹林预孵育可显著抑制EGF-URO诱导的收缩，其效力顺序为（吲哚美辛＞萘普生＞布洛芬＞阿司匹林），这反映了这些药物抑制环氧化酶的能力。3. 数据表明，前列腺素介导了EGF-URO在纵行肌制备中的作用。4. 金诺芬（0.5至50微摩尔），一种用于治疗类风湿性关节炎的具有抗增殖特性的金制剂，也显著抑制了EGF-URO反应；然而，其他含金化合物（30至100微摩尔的硫代葡萄糖金或硫代苹果酸金钠）未能引起显著抑制。5. 用1微摩尔氢化可的松、泼尼松龙或地塞米松对制备物预孵育2小时，可使EGF-URO诱导的收缩抑制约50%。然而，缺乏17α-羟基（皮质酮）或11β-羟基（可的松、脱氧皮质酮、泼尼松）取代基的类固醇不能抑制EGF-URO引起的收缩。对于氢化可的松，抑制作用在0.2微摩尔时达到半数最大，在1微摩尔时达到最大。环己酰亚胺（10微摩尔）阻断了氢化可的松的抑制作用，并增强了EGF-URO的收缩作用。6. 多种甾体和非甾体抗炎药在平滑肌制备物中干扰EGF-URO作用的能力表明，这些药物也可能抑制前列腺素介导的EGF-URO在其他靶组织中的作用。7. 数据还表明EGF-URO在调节胃动力方面可能发挥作用。