英语翻译The low degree,or even absence,of tolerance or dependenc

英语翻译
The low degree,or even absence,of tolerance or dependence
observed after chronic treatment with the dual inhibitors could
be explained by a more specific stimulation of the opioid binding
sites by the tonically released endogenous opioids.A limited
opioid receptor occupation by the endogenous peptides is
supported by in vivo binding studies,which demonstrated that
the increase in tonically released endogenous enkephalins is too
low to saturate opioid receptors.Moreover,chronic morphine
induces a hypersensitivity of noradrenaline-containing
neurons in the locus coeruleus,considered as one of the main
causes of the withdrawal syndrome.It is interesting to observe
that in slices of rat pons,kelatorphan was able to potentiate
strongly the firing of the locus coeruleus that had been induced
by exogenous Met-enkephalin but had no intrinsic effect,indicating
that there is little or no tonic endogenous opioid action
in this brain region .This is probably one of the major reasons
why the withdrawal syndrome is significantly milder after
chronic treatment by dual inhibitors as compared with exogenous
opioids.Indeed,it has been clearly demonstrated that the
locus coeruleus is the most critical structure implicated in the
development of dependence .
On the other hand,an important distinction between opiate
drugs and native peptides is that these two classes of ligand
differ greatly in bioavailability,metabolism and modes of opioid
receptor stimulation (review in [114,115]).This is likely to
account for the observed difference in their potency to induce
tolerance or dependence when they are administered at equieffective
analgesic doses.The poor propensity of a given agonist
to induce tolerance could be linked to its ability to
promote opioid receptor internalization and recycling to the
cell surface in a fully active state,thereby resensitizing cells to
agonist [116,117].Endogenous opioid peptides are typically
released in a phasic or pulsatile manner.Opiate drugs,in contrast,
persist in the extracellular milieu for a prolonged period
of time,and activate opioid receptors in an abnormally prolonged
manner.Opiate drugs that induce rapid desensitization
and endocytosis of receptors may more closely mimic the
phasic actions and physiological adaptations observed with
endogenous opioid peptides.In contrast,opiate drugs such as
morphine,which are unable to induce endocytosis of receptors,
persistently stimulate them,forcing other cellular mechanisms
to compensate at downstream sites for this prolonged
activation.Thus,morphine could have a strongest capability
propensity to cause widespread changes in neural plasticity
associated with drug addiction [118] than the natural
morphine-like peptides.Side effects following chronic treatment
with opiates are probably due to multiple cellular events
involving several components of the cyclic AMP signal
transduction cascade,such as CREB

这种高度专业的文章,机器翻译是应付不了的!
楼主的文章又难又长,要加分哟!
The low degree, or even absence, of tolerance or dependence observed after chronic treatment with the dual inhibitors could be explained by a more specific stimulation of the opioid binding sites by the tonically released endogenous opioids. A limited opioid receptor occupation by the endogenous peptides is supported by in vivo binding studies, which demonstrated that the increase in tonically released endogenous enkephalins is too
low to saturate opioid receptors. Moreover, chronic morphine induces a hypersensitivity of noradrenaline-containing neurons in the locus coeruleus, considered as one of the main causes of the withdrawal syndrome.
通过对鸦片受体结合部位以持续释药内源性鸦片肽进行更特异性的刺激,可得以了解释经过双重抑制剂的长期治疗后所观察到的低度或甚至没有耐性或依赖性的现象.活体内结合研究证实内源性抗菌肽仅有限度地侵占鸦片受体,这表明增加持续释药内源性脑啡肽不足于渗透鸦片受体.而且,长期吗啡中毒所引起蓝斑核中含有去甲肾上腺素的神经细胞的超敏性,也被认为是戒断综合症的原因之一.
It is interesting to observe that in slices of rat pons, kelatorphan was able to potentiate strongly the firing of the locus coeruleus that had been induced by exogenous Met-enkephalin but had no intrinsic effect, indicating that there is little or no tonic endogenous opioid action in this brain region. This is probably one of the major reasons why the withdrawal syndrome is significantly milder after chronic treatment by dual inhibitors as compared with exogenous opioids. Indeed, it has been clearly demonstrated that the locus coeruleus is the most critical structure implicated in the development of dependence.
一个有意思的观测是在大鼠脑桥的切片里,凯拉托芬（注：一种脑啡肽酶抑制药）能够增强刺激由外源性甲硫脑啡肽所引起但没有本质性效应的蓝斑核,这表明脑部只有少许或没有持续内源性鸦片作用.也许这是为何经过双重抑制剂的长期治疗后,其戒断综合症比起外源性鸦片受体显著地比较温和的一个主要原因.确实,这已清楚体现,蓝斑核是依赖性演进中受牵涉的最关键结构.
On the other hand, an important distinction between opiate drugs and native peptides is that these two classes of ligand differ greatly in bioavailability, metabolism and modes of opioid receptor stimulation (review in [114,115]). This is likely to account for the observed difference in their potency to induce tolerance or dependence when they are administered at equieffective analgesic doses. The poor propensity of a given agonist to induce tolerance could be linked to its ability to promote opioid receptor internalization and recycling to the cell surface in a fully active state, thereby resensitizing【应该是desensitizing的笔误】 cells to agonist [116,117].
另一方面,鸦片烟剂与原生肽类最重要的区别是这两个级别的配位体在生物药效率、新陈代谢及鸦片受体的刺激模式都有很大的差距（评论在 [114,115]）.这也许可以解释所观测到当施予同等镇痛剂量时,它们对引发耐性或依赖性的不同效价. 激发剂在极度活性的状态下,能够促进鸦片受体的内在化及再循环至细胞表面,从而使细胞脱敏,这可能是激发剂习性薄弱的原因.[116,117].
Endogenous opioid peptides are typically released in a phasic or pulsatile manner. Opiate drugs, in contrast, persist in the extracellular milieu for a prolonged period of time, and activate opioid receptors in an abnormally prolonged manner. Opiate drugs that induce rapid desensitization and endocytosis of receptors may more closely mimic the phasic actions and physiological adaptations observed with endogenous opioid peptides.
内源性鸦片肽类的一般释药形式是阶段性或搏动性的.相反,鸦片类药物却长时间留在胞外周围,并且以非常延续方式刺激鸦片受体.引发受体的快速脱敏和内吞作用的鸦片类药物,可能更像是模仿对内源性鸦片肽所观测到的阶段性活动及生理适应.
In contrast, opiate drugs such as morphine, which are unable to induce endocytosis of receptors, persistently stimulate them, forcing other cellular mechanisms to compensate at downstream sites for this prolonged activation. Thus, morphine could have a strongest capability propensity to cause widespread changes in neural plasticity associated with drug addiction [118] than the natural morphine-like peptides. Side effects following chronic treatment with opiates are probably due to multiple cellular events involving several components of the cyclic AMP signal transduction cascade, such as CREB
相比之下,鸦片类药物如吗啡,它们不能引发受体的适应,持续不断地刺激受体,强迫其他细胞机理在下游部位来弥补这持续的刺激.因此,比起天然的类吗啡活性肽,吗啡可能是含有最强习性能够造成与药物成瘾相关的神经组织可塑性的广泛变化.[118] 接受鸦片类药物长期治疗导致的副作用可能是因为涉及环状磷酸腺苷信号转导级联多个成分的多重细胞效应的结果,例如合蛋白.
（CREB- cAMP response element-binding protein环状磷酸腺苷反应要素结合蛋白质；简称合蛋白）.
【英语牛人团】
再问： 虽然由于急用我已经自己翻完了，但是看到这么负责认真的答案，真的很感谢。话不多说，100分追加奉上：）以后再有我实在不想翻的段落还找你哈，一定会高分奉上的：）