Pre- and postsynaptic inhibition by nociceptin in guinea pig small intestinal myenteric plexus in vitro.
Pre- and postsynaptic inhibition by nociceptin in guinea pig small intestinal myenteric plexus in vitro.
复制标题
体外伤害感受肽对豚鼠小肠肌间神经丛的突触前和突触后抑制作用。
DOI：
10.1152/ajpgi.2001.281.1.g237
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Wood,JD
中科院分区：
文献类型：
--
作者：
Liu,S;Hu,HZ;Ren,J;Gao,C;Gao,N;Lin,Z;Xia,Y;Wood,JD
用常规方法研究了痛敏素对豚鼠十二指肠肌间神经丛神经元电行为和突触行为的影响。孤啡肽使121个AH型神经元中的104个和51个S型神经元中的28个的膜电位超极化，EC 50为11.9 ± 1.2 nM。增加的K+电导占超极化反应，百日咳毒素和纳洛酮的影响。选择性阿片受体样（ORL）1受体拮抗剂[Phe 1-psi（CH 2-NH）-Gly 2]nociceptin（1-13）-NH 2抑制nociceptin诱发的反应，同时表现为部分激动剂。非选择性ORL 1拮抗剂纳洛酮苯甲酰腙竞争性抑制痛敏作用，pA 2值为5.8。孤啡肽作用于突触前抑制性受体，在30个神经元中的25个中抑制快速兴奋性烟碱突触后电位（EC 50 = 22.5 ± 4.4 nM），在45个神经元中的38个中抑制缓慢突触兴奋（EC 50 = 15.1 ± 1.6 nM）。Nociceptin的突触前抑制作用不受纳洛酮的影响，并被[Phe 1-psi（CH 2-NH）-Gly 2]Nociceptin（1-13）-NH 2或纳洛酮苯甲酰腙拮抗。结果表明，痛敏肽通过激活不同于典型纳洛酮敏感阿片受体的ORL 1受体在突触前和突触后发挥作用。
Actions of nociceptin on electrical and synaptic behavior of morphologically and neurochemically identified neurons in the guinea pig duodenal myenteric plexus were studied with conventional techniques. Nociceptin hyperpolarized the membrane potential in 104 of 121 AH-type and 28 of 51 S-type neurons with an EC50of 11.9 ± 1.2 nM. Increased K+conductance accounted for the hyperpolarizing responses that were blocked by pertussis toxin and unaffected by naloxone. The selective opioid receptor-like (ORL)1receptor antagonist [Phe1-psi(CH2-NH)-Gly2]nociceptin(1–13)-NH2suppressed the nociceptin-evoked responses while behaving like a partial agonist. The nonselective ORL1antagonist naloxone benzoylhydrazone competitively suppressed nociceptin actions with a pA2value of 5.8. Nociceptin acted at presynaptic inhibitory receptors to suppress fast excitatory nicotinic postsynaptic potentials in 25 of 30 neurons (EC50= 22.5 ± 4.4 nM) and slow synaptic excitation in 38 of 45 neurons (EC50= 15.1 ± 1.6 nM). Presynaptic inhibitory action of nociceptin was unaffected by naloxone and was antagonized by [Phe1-psi(CH2-NH)-Gly2]nociceptin(1–13)-NH2or naloxone benzoylhydrazone. The results suggest that nociceptin acts both pre- and postsynaptically by activating an ORL1receptor that is distinct from typical naloxone-sensitive opioid receptors.