Walker J S, Scott C, Bush K A, Kirkham B W
School of Physiology and Pharmacology, University of New South Wales, Sydney NSW, Australia.
Neuropeptides. 2000 Jun-Aug;34(3-4):193-202. doi: 10.1054/npep.2000.0813.
We have previously shown that the kappa-opioid agonist, asimadoline, produces time-dependent changes in neuropeptide concentrations in the joints of rats with chronic arthritis. We hypothesized that asimadoline acts on peripheral terminals to modulate substance P (SP) release. To address this hypothesis, here we have examined neuropeptide expression in their source cells in dorsal root ganglia (DRG) that innervate the joint, as well as in non-neuronal tissue, after treatment with asimadoline. We found an increased production of SP and CGRP in untreated chronic arthritic animals which supports our previous finding of increased SP content in the joint. More importantly, the kappa-opioid asimadoline reduced the expression of both SP and calcitonin gene-related peptide-alpha (alpha-CGRP) in DRG cells but had no effect on the very low expression of neuropeptides in non-neuronal tissue. The fact that SP synthesis is attenuated by asimadoline accords with our hypothesis that the increased tissue levels of SP result from kappa-mediated pre-synaptic inhibition of release leading to augmented tissue stores. These in vivo data confirm literature findings that opioids inhibit SP release from peripheral endings of primary afferent fibres.
我们之前已经表明，κ-阿片受体激动剂阿西马朵林会使慢性关节炎大鼠关节中的神经肽浓度发生时间依赖性变化。我们推测阿西马朵林作用于外周神经末梢来调节P物质（SP）的释放。为了验证这一假设，我们在此研究了用阿西马朵林处理后，支配关节的背根神经节（DRG）中神经肽来源细胞以及非神经组织中的神经肽表达情况。我们发现未经治疗的慢性关节炎动物中SP和降钙素基因相关肽（CGRP）的产生增加，这支持了我们之前关于关节中SP含量增加的发现。更重要的是，κ-阿片受体激动剂阿西马朵林降低了DRG细胞中SP和降钙素基因相关肽-α（α-CGRP）的表达，但对非神经组织中极低水平的神经肽表达没有影响。阿西马朵林减弱SP合成这一事实与我们的假设相符，即SP组织水平升高是由于κ介导的突触前释放抑制导致组织储存增加。这些体内数据证实了文献中的发现，即阿片类药物会抑制初级传入纤维外周末梢释放SP。
