Δ9-tetrahydrocannabinol inhibits gastric motility in the rat through cannabinoid CB1 receptors
Δ9-tetrahydrocannabinol inhibits gastric motility in the rat through cannabinoid CB1 receptors
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DOI：
10.1016/s0014-2999(99)00165-x
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发表时间：
1999-04-29
影响因子：
5
通讯作者：
Hornby, PJ
中科院分区：
文献类型：
--
作者：
Krowicki, ZK;Moerschbaecher, JM;Hornby, PJ
我们研究了自主神经系统参与麻醉大鼠对AG-四氢大麻酚（Delta（9）-THC）的胃运动和心血管反应。腹腔注射Delta（9）-THC可引起胃内压和幽门收缩力的长期降低、心动过缓和低血压。迷走神经切断和神经节阻滞可消除胃运动功能和心动过缓的变化，而脊髓横断可防止肿胀反应。N-（哌啶-1-基）-5-（4-氯苯基）-1-（2，4-二氯苯基）-4-甲基-1H-吡唑-3-甲酰胺（一种假定的大麻素CB 1受体拮抗剂）单独静脉给药可引起胃内压一过性降低和与心动过缓相关的高血压。然而，这种药物完全阻断了静脉注射Delta（9）-THC的胃运动和心血管反应。将Delta（9）-THC应用于延髓背侧表面导致胃运动和心血管功能的小而短暂的降低。我们的结论是，胃运动功能的下降和心动过缓部分是由于在延髓背侧的Delta（9）-THC的作用，并且需要完整的迷走神经。低血压通过交感神经通路介导。外周给药Delta（9）-THC的胃运动和心血管效应似乎都是通过大麻素CB 1受体介导的。(C)1999 Elsevier Science B. V.保留所有权利。
We investigated involvement of the autonomic nervous system in gastric motor and cardiovascular responses to ag-tetrahydrocannabinol (Delta(9)-THC) in anesthetized rats. Intravenously administered Delta(9)-THC evoked long-lasting decreases in intragastric pressure and pyloric contractility, bradycardia, and hypotension. The changes in gastric motor function and bradycardia were abolished by vagotomy and ganglionic blockade, whereas spinal cord transection prevented the hypotensive response. Administered intravenously alone, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, a putative cannabinoid CB1 receptor antagonist, evoked transient decrease in intragastric pressure, and hypertension that was associated with bradycardia. However, this agent completely blocked the gastric motor and cardiovascular responses to intravenous Delta(9)-THC. Application of Delta(9)-THC to the dorsal surface of the medulla resulted in small and short-lasting decreases in gastric motor and cardiovascular function. We conclude that the decrease in gastric motor function and bradycardia are partially due to an action of Delta(9)-THC in the dorsal medulla and that intact vagal nerves are required. The hypotension was mediated through sympathetic pathways. Both gastric motor and cardiovascular effects of peripherally administered Delta(9)-THC seem to be mediated through cannabinoid CB1 receptors. (C) 1999 Elsevier Science B.V. All rights reserved.