Central opiate mu-receptor-mediated suppression of tissue protein synthesis.
Central opiate mu-receptor-mediated suppression of tissue protein synthesis.
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中枢鸦片 mu 受体介导的组织蛋白合成抑制。
DOI：
10.1152/ajpregu.1997.273.3.r920
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Abumrad,NN
中科院分区：
文献类型：
--
作者：
Hashiguchi,Y;Molina,PE;Dorton,S;McNurlan,MA;Garlick,PJ;Reddy,D;Abumrad,NN
我们确定了中枢μ阿片受体刺激对组织蛋白合成速率的剂量依赖性影响。慢性插管清醒大鼠接受脑室内注射[D-Ala 2，N-Me-Phe 4，Gly 5-ol]脑啡肽（DAGO，0.5，2，或8 nmol/rat）或水（5微升）45分钟前确定的蛋白质合成的淹没剂量技术。DAGO使肝脏（57%）、脾脏（54%）、肠粘膜（36%）、肠浆膜（23%）、肾脏（48%）、腓肠肌（33%）和跖肌（27%）中的组织蛋白质合成显著降低，但未改变脑、心脏和比目鱼肌中的蛋白质合成速率。DAGO在脑室内注射后30分钟产生急性剂量依赖性呼吸抑制;该抑制导致酸中毒、缺氧和高碳酸血症（pH 7.19 +/- 0.04，动脉部分O2，压力44.2 +/- 3.4 Torr，动脉O2饱和度65.3 +/-5.5%，PCO 2 66.3 +/- 4.4 Torr）。侧脑室注射DAGO可增加循环中儿茶酚胺、皮质酮和生长激素的水平，但不改变胰岛素和胰岛素样生长因子I的水平。在所研究的组织中观察到蛋白质合成与pH之间的显著正相关性（即，肝脏蛋白质合成与pH值，P < 0.0001，r = 0.902;腓肠肌蛋白质合成与pH值，P < 0.0001，r = 0.830）。我们的研究结果表明，μ受体刺激抑制组织蛋白质的合成，这种效果似乎是次要的呼吸抑制和由此产生的酸中毒和/或缺氧。此外，我们的研究结果表明，不同的敏感性，在pH值的变化，缺氧，应激激素的升高组织反应。
We determined the dose-dependent effects of central mu-opioid receptor stimulation on rates of tissue protein synthesis. Chronically catheterized conscious rats received an intracerebroventricular injection of [D-Ala2, N-Me-Phe4,Gly5-ol]enkephalin (DAGO, 0.5, 2, or 8 nmol/rat) or water (5 microliters) 45 min before determination of protein synthesis by the flooding dose technique. DAGO produced a significant decrease in tissue protein synthesis in liver (57%), spleen (54%), gut mucosa (36%), gut serosa (23%), kidney (48%), gastrocnemius (33%), and plantaris muscle (27%), but it did not alter rates of protein synthesis in the brain, heart, and soleus muscle. DAGO produced an acute dose-dependent respiratory depression 30 min after intracerebroventricular injection; this depression resulted in acidosis, hypoxia, and hypercapnia (pH 7.19 +/- 0.04, arterial partial O2, pressure 44.2 +/- 3.4 Torr, arterial O2 saturation 65.3 +/- 5.5%, and PCO2 66.3 +/- 4.4 Torr). Intracerebroventricular DAGO increased circulating levels of catecholamines, corticosterone, and growth hormone but did not alter those of insulin and insulin-like growth factor I. Significant positive correlations between protein synthesis and pH were observed in the tissues studied (i.e., liver protein synthesis vs. pH, P < 0.0001, r = 0.902; gastrocnemius protein synthesis vs. pH, P < 0.0001, r = 0.830). Our results indicate that mu-receptor stimulation inhibits tissue protein synthesis, and this effect appears to be secondary to respiratory depression and the resulting acidosis and/or hypoxia. Furthermore, our findings suggest differential sensitivity in tissue response to alterations in pH, hypoxia, and stress hormone elevation.