Ozaki N, Sengupta J N, Gebhart G F
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
J Neurophysiol. 2000 Apr;83(4):2209-16. doi: 10.1152/jn.2000.83.4.2209.
Single-fiber recordings were made from the decentralized right cervical vagus nerve (hyponodosal) of the rat. A total of 56 afferent fibers that responded to gastric distension (GD) were studied: 6 fibers were stimulated by phasic balloon GD, 50 by fluid GD. All fibers gave increasing responses to increasing pressures of GD (5-60 mmHg). The effects of mu-opioid (morphine), delta-opioid (SNC80), and kappa-opioid (EMD61,753, U62,066) receptor agonists were tested on responses of afferent fibers to GD. Morphine, administered systemically over a broad dose range (10 microg to 31 mg/kg, cumulative), had no effect on either resting activity or responses of vagal afferent fibers to GD. Similarly, the delta-opioid receptor agonist SNC80 (0.05-3.2 mg/kg) did not affect resting activity or responses to GD. In contrast, cumulative intra-arterial doses of the kappa-opioid receptor agonist EMD61,753 or U62,066 dose dependently attenuated afferent fiber responses to GD. Doses producing inhibition to 50% of the control response to GD of EMD61,753 (8.0 mg/kg) and U62,066 (8.8 mg/kg) did not differ. The effect of U62,066 was moderately attenuated by a nonselective dose (4 mg/kg) of naloxone hydrochloride; the kappa-opioid receptor-selective antagonist nor-BNI (20 mg/kg) was ineffective. These results demonstrate that kappa-, but not mu- or delta-opioid receptor agonists modulate visceral sensation conveyed by vagal afferent fibers innervating the stomach. Given that kappa-opioid receptor agonists effects were only modestly antagonized by naloxone and not at all by nor-BNI, the results point to a novel site of action.
从大鼠去中枢的右侧颈迷走神经（结下神经节）进行单纤维记录。共研究了56条对胃扩张（GD）有反应的传入纤维：6条纤维由阶段性球囊GD刺激，50条由液体GD刺激。所有纤维对GD压力增加（5 - 60 mmHg）均产生增强反应。测试了μ阿片受体（吗啡）、δ阿片受体（SNC80）和κ阿片受体（EMD61,753、U62,066）激动剂对传入纤维对GD反应的影响。在较宽剂量范围（10微克至31毫克/千克，累积给药）全身给予吗啡，对迷走神经传入纤维的静息活动或对GD的反应均无影响。同样，δ阿片受体激动剂SNC80（0.05 - 3.2毫克/千克）不影响静息活动或对GD的反应。相反，κ阿片受体激动剂EMD61,753或U62,066的累积动脉内给药剂量依赖性地减弱了传入纤维对GD的反应。使EMD61,753（8.0毫克/千克）和U62,066（8.8毫克/千克）对GD的对照反应抑制50%的剂量无差异。非选择性剂量（4毫克/千克）的盐酸纳洛酮适度减弱了U62,066的作用；κ阿片受体选择性拮抗剂nor - BNI（20毫克/千克）无效。这些结果表明，κ阿片受体激动剂而非μ或δ阿片受体激动剂调节由支配胃的迷走神经传入纤维传递的内脏感觉。鉴于κ阿片受体激动剂的作用仅被纳洛酮适度拮抗，而未被nor - BNI拮抗，结果指向一个新的作用位点。
