Effect of nociceptin and [Phe1Ψ (CH2–NH) Gly2]-nociceptin-(1–13)-NH2 on tonic activity of rat hypothalamic neurons
Effect of nociceptin and [Phe1Ψ (CH2–NH) Gly2]-nociceptin-(1–13)-NH2 on tonic activity of rat hypothalamic neurons
复制标题
伤害感受肽和[Phe1Ψ (CH2–NH) Gly2]-伤害感受肽-(1–13)-NH2对大鼠下丘脑神经元强直活性的影响
DOI：
10.1016/s0304-3940(99)00684-9
复制
发表时间：
1999
影响因子：
2.5
通讯作者：
F. Pierau
中科院分区：
文献类型：
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作者：
K. Yakimova;F. Pierau
孤啡肽是克隆的阿片受体家族ORL 1-受体的一个独特成员的内源性配体，它对视前区/下丘脑前部（PO/AH）神经元的紧张性活动的影响已在大鼠脑切片中使用细胞外记录进行了研究。孤啡肽（1，10和100 nM）剂量依赖性地降低PO/AH神经元的紧张性活动。该作用与最近提出作为伤害感受素受体的选择性拮抗剂的[Phe 1-（CH 2-NH）Gly 2]-伤害感受素-（1-13）-NH 2（1、10和100 nM）的作用没有显著不同。因此，[Phe 1-（CH 2-NH）Gly 2]-nociceptin-（1-13）-NH 2在大鼠PO/AH神经元上似乎是孤啡肽（ORL 1）受体的激动剂而不是拮抗剂。然而，当伤害感受素和[Phe 1-（CH 2-NH）Gly 2]-伤害感受素-（1-13）-NH 2以等摩尔浓度同时应用时，既没有拮抗作用，也没有相加协同作用。选择性μ-、κ-和δ-阿片受体拮抗剂（d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH 2（CTOP）、nor-binaltorphimine和naltrindol）在高10倍浓度时均不能阻断孤啡肽对大鼠PO/AH神经元张力活动的影响。这些数据表明，孤啡肽对PO/AH神经元的紧张性活动的影响不是由于对μ-，κ-或δ-阿片受体的作用，而是由于对ORL 1受体的特异性作用。
The effect of nociceptin, an endogenous ligand for a unique member of the cloned opioid receptor family ORL1-receptor, on tonic activity of neurons in the preoptic area/anterior hypothalamus (PO/AH) has been examined in rat brain slices using extracellular recordings. Nociceptin (1, 10 and 100 nM) decreased dose-dependently tonic activity of PO/AH neurons. This effect was not significantly different from the effect of [Phe1Ψ (CH2–NH) Gly2]-nociceptin-(1–13)-NH2(1, 10 and 100 nM), recently proposed as a selective antagonist of the nociceptin receptor. Thus, [Phe1Ψ (CH2–NH) Gly2]-nociceptin-(1–13)-NH2appears to be an agonist rather than an antagonist of nociceptin (ORL1) receptor in rat PO/AH neurons. However, there was neither antagonism nor additive synergism when nociceptin and [Phe1Ψ (CH2–NH) Gly2]-nociceptin-(1–13)-NH2were applied simultaneously at equimolar concentrations. The effect of nociceptin on tonic activity of rat PO/AH neurons was not blocked by selective μ-, κ- and δ-opioid receptor antagonists (d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2(CTOP), nor-binaltorphimine and naltrindol, respectively) at 10 times higher concentrations than nociceptin. These data suggest that the effect of nociceptin on tonic activity of PO/AH neurons is not due to an action on μ-, κ-, or δ-opioid receptors but results from a specific effect on the ORL1-receptor.
DOI：
--
发表时间：
1997-08
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
G. Rossi;L. Leventhal;E. Bolan;G. Pasternak
通讯作者：
G. Rossi;L. Leventhal;E. Bolan;G. Pasternak
纳洛酮敏感孤啡肽 FQ 诱导的小鼠镇痛。
影响因子：
5
作者：
Rossi,GC;Leventhal,L;Pasternak,GW
通讯作者：
Pasternak,GW