Kvetnansky Richard
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06 Bratislava, Slovak Republic.
Ann N Y Acad Sci. 2004 Dec;1032:117-29. doi: 10.1196/annals.1314.009.
The specific activation of two components of the sympathoadrenal system (adrenomedullary and sympathoneural) by various stressors was recently described. The aim of this work was to investigate changes in catecholamine (CA) biosynthetic enzyme phenylethanolamine N-methyltransferase (PNMT) gene expression, protein level, and activity in the adrenal medulla of rats after a single or repeated exposure to various homotypic or novel heterotypic stressors. Immobilization for 2 h (IMO), cold 4 degrees C (COLD), administration of insulin 5I U (INS), or 2-deoxyglucose 500 mg/kg (2DG) were used as stressors. Plasma epinephrine (EPI) and norepinephrine (NE) levels clearly showed that these stressors specifically activate the aforementioned systems. A single exposure to IMO, COLD, INS, or 2DG induced increases in PNMT mRNA levels in the adrenal medulla. Besides PNMT mRNA, repeated exposure to IMO also elevated activity and protein levels of the enzyme; however, chronic cold exposure did not show PNMT changes compared to control animals at room temperature. PNMT gene expression was also investigated in rats adapted to repeated immobilization stress or to chronic cold exposure after a single exposure to various heterotypic novel stressors. Cold-adapted rats responded to heterotypic novel stressors (IMO, INS) by exaggerated responses of PNMT mRNA levels compared to responses in naive rats exposed to the same stressors at room temperature. Immobilization-adapted rats did not show exaggerated responses of PNMT mRNA after exposure to novel stressors. Therefore, observed differences in plasma CA and adrenomedullary mRNA levels suggest a specific regulation of CA release, synthesis, and gene expression of CA biosynthetic enzymes, which depends on the quality of the stressor. Exposure of adapted rats to novel stressors induces exaggerated responses, but this process also depends on the specificity of the stressor used. Different stressors regulate PNMT gene expression by specific mechanisms especially in chronically stressed rats. These mechanisms remain to be elucidated. It is the ability of the long-term stressed organism to respond differently to novel heterotypic stressors that we consider an important adaptive phenomenon of catecholaminergic systems in rats.
最近有研究描述了各种应激源对交感肾上腺系统两个组成部分(肾上腺髓质和交感神经)的特异性激活作用。本研究的目的是探究单次或反复暴露于各种同型或新型异型应激源后,大鼠肾上腺髓质中儿茶酚胺(CA)生物合成酶苯乙醇胺N -甲基转移酶(PNMT)的基因表达、蛋白水平及活性的变化。采用2小时固定(IMO)、4℃冷刺激(COLD)、5IU胰岛素注射(INS)或500mg/kg 2 -脱氧葡萄糖注射(2DG)作为应激源。血浆肾上腺素(EPI)和去甲肾上腺素(NE)水平清楚地表明,这些应激源特异性激活了上述系统。单次暴露于IMO、COLD、INS或2DG均可诱导肾上腺髓质中PNMT mRNA水平升高。除了PNMT mRNA外,反复暴露于IMO还可提高该酶的活性和蛋白水平;然而,与室温下的对照动物相比,长期冷暴露并未显示PNMT有变化。在单次暴露于各种异型新型应激源后,还对适应反复固定应激或长期冷暴露的大鼠的PNMT基因表达进行了研究。与室温下暴露于相同应激源的未适应大鼠相比,冷适应大鼠对异型新型应激源(IMO、INS)的反应是PNMT mRNA水平的过度升高。适应固定应激的大鼠在暴露于新型应激源后未显示PNMT mRNA的过度反应。因此,观察到的血浆CA和肾上腺髓质mRNA水平的差异表明,CA释放、合成及CA生物合成酶基因表达存在特异性调节,这取决于应激源的性质。使适应的大鼠暴露于新型应激源会诱导过度反应,但这一过程也取决于所用应激源的特异性。不同的应激源通过特定机制调节PNMT基因表达,尤其是在长期应激的大鼠中。这些机制仍有待阐明。我们认为长期应激生物体对新型异型应激源做出不同反应的能力是大鼠儿茶酚胺能系统的一种重要适应性现象。