首页> 外文期刊>American Journal of Physiology >micro-Opioid receptor stimulation in the medial subnucleus of the tractus solitarius inhibits gastric tone and motility by reducing local GABA activity.
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micro-Opioid receptor stimulation in the medial subnucleus of the tractus solitarius inhibits gastric tone and motility by reducing local GABA activity.

机译:孤束腹内侧亚核中的微阿片受体刺激通过降低局部GABA活性抑制胃音和运动性。

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We examined the effects of altering mu-opioid receptor (MOR) activity in the medial subnucleus of the tractus solitarius (mNTS) on several gastric end points including intragastric pressure (IGP), fundus tone, and the receptive relaxation reflex (RRR). Microinjection of the MOR agonist [d-Ala(2),MePhe(4),Gly(ol)(5)]enkephalin (DAMGO; 1-10 fmol) into the mNTS produced dose-dependent decreases in IGP. Microinjection of the endogenous MOR agonists endomorphin-1 and endomorphin-2 (20 fmol) into the mNTS mimicked the effects of 10 fmol DAMGO. Microinjection of 1 and 100 pmol DAMGO into the mNTS produced a triphasic response consisting of an initial decrease, a transient increase, and a persistent decrease in IGP. The increase in IGP appeared to be due to diffusion to the dorsal motor nucleus of the vagus. The effects of 10 fmol DAMGO in the mNTS were blocked by vagotomy and by blockade of MORs, GABA(A) receptors, and ionotropic glutamate receptors in the mNTS. The RRR response was abolished by bilateral microinjection of the opioid receptor antagonist naltrexone into the mNTS and reduced by intravenous administration of naltrexone. Our data demonstrate that 1) activation of MORs in the mNTS with femtomole doses of agonist inhibits gastric motility, 2) the mechanism of MOR effects in the mNTS is through suppression of local GABA activity, and 3) blockade of MORs in the mNTS prevents the RRR response. These data suggest that opioids play an important role in mediating a vagovagal reflex through release of an endogenous opioid in the mNTS, which, in turn, inhibits ongoing local GABA activity and allows vagal sensory input to excite second-order mNTS neurons.
机译:我们检查了改变孤束腹内侧亚核(mNTS)中的μ阿片受体(MOR)活性对几个胃端点的影响,包括胃内压(IGP),眼底张力和感受性松弛反射(RRR)。向mNTS中微量注射MOR激动剂[d-Ala(2),MePhe(4),Gly(ol)(5)]脑啡肽(DAMGO; 1-10 fmol)在IGP中产生剂量依赖性降低。将内源性MOR激动剂endomorphin-1和endomorphin-2(20 fmol)显微注射到mNTS中可模拟10 fmol DAMGO的作用。向mNTS中微量注射1和100 pmol DAMGO会产生三重反应,包括初始降低,瞬时升高和IGP持续降低。 IGP的增加似乎是由于扩散到迷走神经的背运动核。 10 fmol DAMGO在mNTS中的作用被迷走神经切断术和mNTS中的MOR,GABA(A)受体和离子型谷氨酸受体阻断。通过将阿片样物质受体拮抗剂纳曲酮双侧显微注射到mNTS中,RRR反应被消除,而通过静脉注射纳曲酮,RRR反应被降低。我们的数据表明,1)用飞摩尔剂量的激动剂激活mNTS中的MORs可以抑制胃动力,2)mNTS中MOR的作用机理是通过抑制局部GABA活性,以及​​3)阻断mNTS中的MORs可以预防胃癌的发生。 $$响应。这些数据表明,阿片类药物通过释放mNTS中的内源性阿片类药物在介导迷走神经反射中起重要作用,继而抑制正在进行的局部GABA活性,并允许迷走神经感觉输入激发二阶mNTS神经元。

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