Zhou Peilan, Li Yulei, Yong Zheng, Yan Hui, Su Ruibin, Gong Zehui
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, Beijing 100850, China.
Eur J Pharmacol. 2016 Oct 15;789:144-151. doi: 10.1016/j.ejphar.2016.07.029. Epub 2016 Jul 18.
Opioid analgesics are widely used in moderate to severe pain including renal colic. Morphine is believed to cause spasm of ureter and affect the bladder contractions. Thienorphine is a partial opioid agonist that is a good candidate for the treatment of opioid dependence and pain. This study examined the effects of thienorphine on the guinea pig isolated ureter and bladder. The contractile amplitude of isolated ureter induced by KCl (40mM) was not influenced by thienorphine or buprenorphine, whereas morphine increased the amplitude of the isolated ureter. Thienorphine, buprenorphine or naloxone concentration-dependently antagonized the isolated ureter contraction induced by morphine. Thienorphine (1.0-32.0μM) or buprenorphine (1.0-32.0μM) had no effects on the spontaneous or acetylcholine (Ach) induced contractions of isolated bladder, but decreased the amplitude of the contractions of isolated bladder at 100μM concentration. Morphine (0.1-3.2mM) concentration dependently increased the spontaneous movement and Ach (1μM) induced contractions of isolated bladder. The mRNA levels of μ receptor in the ureter and bladder was as the same as that in the frontal cortex. In comparison, the mRNA levels of κ receptor, δ receptor and N/OFQ receptor was fewer than that in the frontal cortex. In summary, thienorphine has little influence on the guinea pig isolated ureter and bladder compared with morphine, which may result in a lack of adverse renal colic effects.
阿片类镇痛药广泛用于包括肾绞痛在内的中重度疼痛。吗啡被认为会引起输尿管痉挛并影响膀胱收缩。噻诺啡是一种部分阿片类激动剂，是治疗阿片类药物依赖和疼痛的良好候选药物。本研究考察了噻诺啡对豚鼠离体输尿管和膀胱的作用。氯化钾（40mM）诱导的离体输尿管收缩幅度不受噻诺啡或丁丙诺啡影响，而吗啡可增加离体输尿管的收缩幅度。噻诺啡、丁丙诺啡或纳洛酮可浓度依赖性地拮抗吗啡诱导的离体输尿管收缩。噻诺啡（1.0 - 32.0μM）或丁丙诺啡（1.0 - 32.0μM）对离体膀胱的自发收缩或乙酰胆碱（Ach）诱导的收缩无影响，但在100μM浓度时可降低离体膀胱的收缩幅度。吗啡（0.1 - 3.2mM）浓度依赖性地增加离体膀胱的自发活动和Ach（1μM）诱导的收缩。输尿管和膀胱中μ受体的mRNA水平与额叶皮质中的相同。相比之下，κ受体、δ受体和孤啡肽受体的mRNA水平低于额叶皮质。总之，与吗啡相比，噻诺啡对豚鼠离体输尿管和膀胱影响较小，这可能导致其缺乏肾绞痛不良影响。
