Tian Xiao-zhu, Chen Juan, Xiong Wei, He Tian, Chen Qiang
Department of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China.
Peptides. 2009 Jul;30(7):1348-54. doi: 10.1016/j.peptides.2009.04.002. Epub 2009 Apr 10.
In the present study, we investigated the effects of human opiorphin on colonic motility and nociception in mice. In in vitro bioassay, opiorphin (10(-6) to 10(-4)M) caused colonic contraction in a concentration-dependent manner, which was completely blocked by naloxone and partially attenuated by beta-funaltrexamine and naltrindole. Moreover, opiorphin (10(-4)M) significantly enhanced the contractile response induced by Met-enkephalin. The data suggested that the effect of opiorphin on colonic contraction may be due to the protection of enkephalins. In in vivo bioassay, intracerebroventricular (i.c.v.) administration of opiorphin (1.25-10 microg/kg) dose- and time-dependently induced potent analgesic effect (ED(50)=3.22 microg/kg). This effect was fully blocked by naloxone and significantly inhibited by co-injection (i.c.v.) with beta-funaltrexamine or naltrindole, but not by nor-binaltorphimine, indicating the involvement of both mu- and delta-opioid receptors in the analgesic response evoked by opiorphin. In addition, i.c.v. administration of 5 microg/kg opiorphin produced the comparative effect as 10 microg/kg morphine on the analgesia, suggesting that opiorphin displayed more potent analgesic effect than that induced by morphine.
在本研究中，我们调查了人源阿片素对小鼠结肠运动性和痛觉的影响。在体外生物测定中，阿片素（10⁻⁶至10⁻⁴M）以浓度依赖性方式引起结肠收缩，这被纳洛酮完全阻断，并被β-氟纳曲酮和纳曲吲哚部分减弱。此外，阿片素（10⁻⁴M）显著增强了甲硫氨酸脑啡肽诱导的收缩反应。数据表明，阿片素对结肠收缩的作用可能归因于对脑啡肽的保护。在体内生物测定中，脑室内（i.c.v.）注射阿片素（1.25 - 10微克/千克）剂量和时间依赖性地诱导出强效镇痛作用（ED₅₀ = 3.22微克/千克）。这种作用被纳洛酮完全阻断，并被与β-氟纳曲酮或纳曲吲哚共同注射（i.c.v.）显著抑制，但不被去甲二氢吗啡酮抑制，表明μ和δ阿片受体均参与了阿片素诱发的镇痛反应。此外，i.c.v.注射5微克/千克阿片素产生的镇痛效果与10微克/千克吗啡相当，表明阿片素显示出比吗啡诱导的更强效镇痛作用。
