Fox A J, Morton I K
Divison of Biomedical Sciences, King's College London, UK.
Naunyn Schmiedebergs Arch Pharmacol. 1991 Jul;344(1):8-15. doi: 10.1007/BF00167377.
The effects of three different opioid agonists on contractions and [3H]-acetylcholine (ACh) release evoked by 5-hydroxytryptamine3 (5-HT3) and neurokinin-3 (NK-3) receptor activation were examined in the guinea-pig ileum longitudinal muscle-myenteric plexus strip (LMMP) preparation. The selective mu (mu)-opioid receptor agonist (D-Ala2,NMe-Phe4,Gly-ol]-enkephalin (DAMGO; 1 nM-100 nM) and the selective kappa (kappa)-opioid receptor agonist U50488 (10 nM-1 microM) inhibited contractile responses to 5-HT and to the selective NK-3 receptor agonist senktide, producing a concentration-related progressive flattening of their concentration-response curves. IC50 estimates for DAMGO and U50488 were somewhat higher for inhibition of 5-HT-evoked as compared to senktide-evoked contractions, and overall lay in the range 6 nM-51 nM. The selective delta (delta)-opioid receptor agonist [D-Pen2,5]-enkephalin (DPDPE) inhibited contractile responses only at the highest concentration used (1 microM). 3H-overflow from LMMP preparations preincubated with [3H]-choline was measured as an indicator of [3H]-ACh release. DAMGO (1 nM-100 nM) and U50488 (10 nM-1 microM) inhibited the increases in release of [3H]-ACh evoked by 5-HT (10 microM) and by senktide (10 nM) in a concentration-dependent manner. IC50 estimates for DAMGO and U50488 were not significantly different for inhibition of 5-HT as compared to senktide-evoked increases in [3H]-ACh release and lay in the range 6 nM-23 nM. DPDPE again only inhibited these responses at the maximum concentration used (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
在豚鼠回肠纵行肌-肌间神经丛条（LMMP）标本中，研究了三种不同阿片类激动剂对由5-羟色胺3（5-HT3）和神经激肽-3（NK-3）受体激活所诱发的收缩及[3H]-乙酰胆碱（ACh）释放的影响。选择性μ（mu）-阿片受体激动剂（D-Ala2，NMe-Phe4，Gly-ol]-脑啡肽（DAMGO；1 nM - 100 nM）和选择性κ（kappa）-阿片受体激动剂U50488（10 nM - 1 μM）抑制了对5-HT以及选择性NK-3受体激动剂senktide 的收缩反应，使其浓度-反应曲线呈浓度相关的逐渐变平。与抑制senktide诱发的收缩相比，DAMGO和U50488对5-HT诱发收缩的IC50估计值略高，总体范围在6 nM - 51 nM。选择性δ（delta）-阿片受体激动剂[D-Pen2,5]-脑啡肽（DPDPE）仅在所用最高浓度（1 μM）时抑制收缩反应。用[3H]-胆碱预孵育的LMMP标本中的3H溢出量被测定作为[3H]-ACh释放的指标。DAMGO（1 nM - 100 nM）和U50488（10 nM - 1 μM）以浓度依赖性方式抑制了由5-HT（10 μM）和senktide（10 nM）诱发的[3H]-ACh释放增加。与抑制senktide诱发的[3H]-ACh释放增加相比，DAMGO和U50488对5-HT抑制的IC50估计值无显著差异，范围在6 nM - 23 nM。DPDPE同样仅在所用最大浓度（1 μM）时抑制这些反应。（摘要截断于250字）
