摘要
阿片类药物是至今最有效的镇痛药,但是长期应用会产生药物耐受,大大限制了其临床应用。μ阿片受体和特定的激动剂结合后会出现内吞。研究发现,μ阿片受体是否内吞与耐受的发生有密切关系;加强μ阿片受体的内吞能够抑制受体耐受。不同的激动剂导致μ阿片受体内吞的能力是不同的;其导致耐受的能力和导致内吞的能力呈负相关。激动剂越容易引起μ受体内吞,就越不容易产生吗啡耐受。内吞的作用在于能抑制过度刺激μ受体而导致的环腺苷酸(cyclicadenosine monophosphate,cAMP)等兴奋性信号通路的激活,而内吞的μ受体也会很快回到细胞膜上,恢复和阿片类药物结合后激活抑制性GTP结合蛋白的能力。因此,对受体的内吞和其后迁移过程展开研究,可能为慢性疼痛的治疗找到新的路径。
Opioids are the most effective analgesics.However,prolonged administration of morphine,the representative of opioids,results in tolerance,limiting the therapeutic utility of opiate drugs.Studies have recently suggested that endocytosis of μ opioid receptors attenuates opioid tolerance.The ability of inducing endocytosis of opioid receptor is agonist-dependent.It has been shown that the endocytotic efficacy of opioids are negatively correlated with opioid tolerance.Receptor internalization reduced adaptive changes in signaling pathways that are involved in the development of opioid tolerance.Moreover,endocytosised μ-opioid receptors are rapidly recycled back to the cell membrane surface resuming their normal function.Therefore,tolerance does not occur.Thus,the study of receptor endocytosis and trafficking following the activation of the receptors can help the therapy for chronic pain.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2012年第10期1185-1190,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金资助项目(30970985
31171072)
关键词
Μ阿片受体
吗啡耐受
受体内吞
GTP结合蛋白信号通路
μ opioid receptors
Morphine tolerance
Receptor internalization
G protein signaling pathways
