摘要
研究了阿片类药物在豚鼠离体回肠中的交互依赖性和交互耐受性．豚鼠回肠分别与羟甲芬太尼（ＯＭＦ１ｎｍｏｌ·Ｌ－１），Ｄ－Ａｌａ２，Ｄ－Ｌｅｕ５－脑啡肽（ＤＡＤＬＥ，０．３μｍｏｌ·Ｌ－１）或Ｕ５０４８８Ｈ（５０ｎｍｏｌ·Ｌ－１）在３７℃温育４ｈ，它们相互及自身均能抑制纳洛酮（０．１μｍｏｌ·Ｌ－１）或Ｍｒ２２６６（０．１μｍｏｌ·Ｌ－１）引起的戒断性收缩．它们也能自身预先阻断戒断性收缩的产生．Ｕ５０４８８Ｈ能预先阻断ＯＭＦ，ＤＡＤＬＥ温育后纳洛酮所产生的戒断性收缩，但后两者不能预先阻断Ｕ５０４８８Ｈ温育后由Ｍｒ２２６６所产生的戒断性收缩，并且ＯＭＦ和ＤＡＤＬＥ之间也不能相互阻断．豚鼠回肠分别与ＯＭＦ（１ｎｍｏｌ·Ｌ－１），ＤＡＤＬＥ（０．３μｍｏｌ·Ｌ－１）在３７℃温育２ｈ后，对去甲吗啡（ＮＭ），ＯＭＦ，ＤＡＤＬＥ的敏感性明显下降，浓度反应曲线右移，但对Ｕ５０４８８Ｈ不产生耐受．在Ｕ５０４８８Ｈ（１０ｎｍｏｌ·Ｌ－１）中温育１ｈ的回肠，对Ｕ５０４８８Ｈ的敏感性下降，浓度反应曲线右移，但对ＯＭＦ，ＮＭ，ＤＡＤＬＥ的敏感性不变．这些结果表明豚鼠回肠中μ，κ阿片受体是分离的．
Cross dependence and cross tolerance of opioids in the guinea pig isolated ileum have been studied. After incubated with ohmefentanyl (OMF, 1 nmol·L 1 ), D Ala 2, D Leu 5 enkephalin (DADLE, 0.3 μmol·L 1 ) or trans 3,4 dichloro N methyl N [2 (1 pyrrolidinyl)cyclohexyl] benzeneacetamide(U50488H, 50 nmol·L 1 ) at 37℃ for 4 h, the withdrawal contractions of the guinea pig ileum precipitated by naloxone (0.1 μmol·L 1 )or Mr2266 (0.1 μmol·L 1 ) could be inhibited by these drugs. The withdrawal contractions precipitated by naloxone in the segments of the ileum incubated with OMF were blocked by pretreatment of OMF or U50488H but not by DADLE. The withdrawal contractions precipitated by naloxone in the segments incubated with DADLE were blocked by pretreatment of DADLE or U50488H but not by OMF. Only U50488H could block the production of withdrawal contraction precipitated by Mr2266 (0.1 μmol·L 1 ) in the ileum incubated with U50488H. In cross tolerance experiments, after the segment of the ileum was incubated with OMF (1 nmol·L 1 ) or DADLE (0.3 μmol·L 1 ) at 37℃ for 2 h, the sensitivities of the preparations for normorphine (NM), OMF and DADLE were reduced significantly, their concentration response curves were shift to right. But these segments of ileum did not produce tolerance for U50488H. In the segments of ileum incubated with U50488H (10 nmol·L 1 ) for 1 h, the sensitivity for U50488H was reduced, the concentration response curve was shift to right, but the sensitivities for OMF, NM and DADLE were unchanged. These results suggest that μ and κ opioid receptors in the guinea pig ileum be dissociative.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
1998年第4期271-274,共4页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金
关键词
回肠
药物耐受性
阿片药物
药物相互作用
guinea pigs
ileum
narcotic dependence
drug tolerance
drug interactions
