Danks J A, Tortella F C, Long J B, Bykov V, Jacobson A E, Rice K C, Holaday J W, Rothman R B
Laboratory of Preclinical Pharmacology, NIMH, St. Elizabeths Hospital, Washington, DC 20002.
Neuropharmacology. 1988 Sep;27(9):965-74. doi: 10.1016/0028-3908(88)90125-6.
Previous studies have demonstrated that chronic administration of morphine up-regulated the lower affinity binding site for [3H][D-ala2,D-leu5]enkephalin, without producing a detectable alteration in the higher affinity binding site for [3H][D-ala2,D-leu5]enkephalin (Rothman et al., Eur. J. Pharmac. 124: 113-119, 1986). The experiments reported in this paper tested the hypothesis that chronic administration of morphine and naltrexone up-regulated the binding sites for [3H][D-ala2,D-leu5]enkephalin by different mechanisms. Rats were given either morphine or naltrexone chronically. Chronic administration of morphine up-regulated the lower affinity site, while chronic administration of naltrexone up-regulated both the higher and lower affinity binding sites for [3H][D-ala2,D-leu5]enkephalin. Unlike the lower affinity binding site for [3H][D-ala2,D-leu5]enkephalin present in membranes prepared from rats treated with placebo pellets, the lower affinity binding sites which were up-regulated by naltrexone and morphine were partially (naltrexone) or completely (morphine) labile to preincubation for 60 min at 25 degrees C in 50 mM Tris-HCl, pH 7.4, containing 0.4 M NaCl. These data suggest that chronic administration of morphine and naltrexone up-regulate binding sites for [3H][D-ala2,D-leu5]enkephalin through different mechanisms, and that the lower affinity binding sites for [3H][D-ala2, D-leu5]enkephalin which are up-regulated by chronic administration of morphine and naltrexone might differ biochemically from the lower affinity binding sites present in membranes treated with placebo.
先前的研究表明，长期给予吗啡可上调[3H][D-丙氨酸2，D-亮氨酸5]脑啡肽的低亲和力结合位点，而[3H][D-丙氨酸2，D-亮氨酸5]脑啡肽的高亲和力结合位点未出现可检测到的改变（罗斯曼等人，《欧洲药理学杂志》124：113 - 119，1986年）。本文报道的实验检验了以下假说：长期给予吗啡和纳曲酮通过不同机制上调[3H][D-丙氨酸2，D-亮氨酸5]脑啡肽的结合位点。大鼠被长期给予吗啡或纳曲酮。长期给予吗啡可上调低亲和力位点，而长期给予纳曲酮则上调[3H][D-丙氨酸2，D-亮氨酸5]脑啡肽的高亲和力和低亲和力结合位点。与用安慰剂丸剂处理的大鼠制备的膜中存在的[3H][D-丙氨酸2，D-亮氨酸5]脑啡肽的低亲和力结合位点不同，由纳曲酮和吗啡上调的低亲和力结合位点在含有0.4M氯化钠的50mM Tris-HCl（pH 7.4）中于25℃预孵育60分钟后，部分（纳曲酮）或完全（吗啡）不稳定。这些数据表明，长期给予吗啡和纳曲酮通过不同机制上调[3H][D-丙氨酸2，D-亮氨酸5]脑啡肽的结合位点，并且长期给予吗啡和纳曲酮上调的[3H][D-丙氨酸2，D-亮氨酸5]脑啡肽的低亲和力结合位点在生化性质上可能与用安慰剂处理的膜中存在的低亲和力结合位点不同。
