Yuan C S
Committee on Clinical Pharmacology, University of Chicago Medical Center, IL 60637, USA.
Eur J Pharmacol. 1996 Oct 24;314(1-2):27-32. doi: 10.1016/s0014-2999(96)00531-6.
Single units in the medial subnucleus of the nucleus tractus solitarii, responding to electrical stimulation of subdiaphragmatic vagal fibers, were recorded extracellularly in an in vitro neonatal rat brainstem-gastric preparation. Selective opioid receptor agonists were applied only to the gastric compartment of the bath chamber and therefore, the brainstem functions of the preparation were not affected. The peripheral gastric effects of the mu-opioid receptor agonist, [D-Ala2, N-MePhe4, Gly5-ol]enkephalin (DAMGO) and kappa-opioid receptor agonist, ¿trans-3,4-dichloro-N-methyl-N-[2-(l-pyrrolidinyl)cyclohexyl]cyclohexyl] benzeneacetamide methanesulfonate hydrate¿ (U-50, 488H), were evaluated on 69 units that received the subdiaphragmatic vagal input. For approximately 75% of the units observed, DAMGO (1.0 microM; IC70; 80 nM) and U-50, 488H (1.0 microM; IC70:200 nM) induced a concentration-dependent inhibition of 62.7 +/- 8.9% (mean +/- S.D.) and 50.6 +/- 6.2% of the control level of the brainstem neuronal activity, respectively. The mu-opioid selective receptor antagonist, naltrexone and non-selective opioid receptor antagonist, naloxone, respectively, blocked the inhibitory effects by DAMGO and U-50, 488 H. The delta-opioid receptor agonist, [D-Pen2, D-Pen5]enkephalin (DPDPE) (10 microM; IC70:400 nM) produced a lesser extent of inhibition of 21.9 +/- 8.0% in the only 10 out of 51 (20%) neurons tested, and this effect was blocked by naloxone. The area of the stomach where gastric opioid receptors contributed most to brainstem unitary activity was also examined. This was achieved by comparing the opioid effects on a whole-stomach preparation to its effects on a partial-stomach preparation. Our data indicated that the distal stomach containing the pylorus played a key role in the gastric effects of mu- and kappa-opioid receptors on brainstem neuronal activity. These results suggest that the mu- and kappa-opioid receptors of the distal stomach are important in modulation of brainstem neuronal activity and may play a role in regulating the digestive process.
在新生大鼠离体脑干-胃标本中，细胞外记录孤束核内侧亚核中对膈下迷走神经纤维电刺激有反应的单个神经元。选择性阿片受体激动剂仅施加于浴槽腔的胃部分，因此该标本的脑干功能未受影响。评估了μ-阿片受体激动剂[D-丙氨酸²，N-甲基苯丙氨酸⁴，甘氨酸⁵-醇]脑啡肽（DAMGO）和κ-阿片受体激动剂反式-3,4-二氯-N-甲基-N-[2-(1-吡咯烷基)环己基]环己基]苯乙酰胺甲磺酸盐一水合物（U-50,488H）对69个接受膈下迷走神经输入的神经元的外周胃效应。在观察到的约75%的神经元中，DAMGO（1.0微摩尔；IC70；80纳摩尔）和U-50,488H（1.0微摩尔；IC70:200纳摩尔）分别引起脑干神经元活动对照水平浓度依赖性抑制，抑制率分别为62.7±8.9%（平均值±标准差）和50.6±6.2%。μ-阿片选择性受体拮抗剂纳曲酮和非选择性阿片受体拮抗剂纳洛酮分别阻断了DAMGO和U-50,488H的抑制作用。δ-阿片受体激动剂[D-青霉胺²，D-青霉胺⁵]脑啡肽（DPDPE）（10微摩尔；IC70:400纳摩尔）在51个（20%）测试神经元中仅10个中产生了较小程度的抑制，抑制率为21.9±8.0%，且该效应被纳洛酮阻断。还研究了胃中阿片受体对脑干单位活动贡献最大的区域。这是通过比较阿片对全胃标本的作用与其对部分胃标本的作用来实现的。我们的数据表明，含有幽门的胃远端在μ-和κ-阿片受体对脑干神经元活动的胃效应中起关键作用。这些结果表明，胃远端的μ-和κ-阿片受体在调节脑干神经元活动中很重要，可能在调节消化过程中发挥作用。
