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首页> 外文期刊>Neurobiology of learning and memory >Nociceptin and its metabolite attenuate U0126-induced memory impairment through a nociceptin opioid peptide (NOP) receptor-independent mechanism.
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Nociceptin and its metabolite attenuate U0126-induced memory impairment through a nociceptin opioid peptide (NOP) receptor-independent mechanism.

机译：Nociceptin及其代谢产物通过Nociceptin阿片肽（NOP）受体独立机制减轻U0126-诱导的记忆障碍。

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摘要

Nociceptin binds to nociceptin opioid peptide (NOP) receptors. We reported that although high doses of nociceptin impaired memory function and that these effects were mediated via NOP receptors, low doses of nociceptin attenuated the memory impairment, and these attenuating effects were not mediated via NOP receptors. Even very low doses of nociceptin were biologically active and suggested a certain binding site for this peptide, but the mechanism underlying this attenuating effect has not yet been elucidated. In the present study, we investigated the effect of an intrahippocampal injection (i.h.) of nociceptin on memory impairment induced by U0126, a MEK inhibitor, and Rp-cAMPS, a PKA inhibitor in a step-down type passive avoidance test. U0126 (2.63 nmol/mouse, i.h.) impaired memory formation and training-dependent phosphorylation of ERK2 in the hippocampus. Co-administration of nociceptin (10 fmol/mouse) significantly attenuated memory impairment, while it did not attenuate the inhibition of training-dependent phosphorylation of ERK2 induced by U0126. On the other hand, nociceptin did not attenuate memory impairment induced by Rp-cAMPS (0.448 nmol/mouse, i.h.). Nociceptin (1 fmol/mouse) also attenuated U0126 (5.26 nmol/mouse)-induced memory impairment in NOP receptor knockout mice. Nociceptin was reported to metabolize into fragments (1-13) and (14-17) in vivo, which showed pharmacological activities without affecting NOP receptors. Our findings showed that nociceptin (14-17) (1 fmol/mouse) also attenuated U0126-induced memory impairment, while nociceptin (1-13) (0.1-10 fmol/mouse) did not attenuate memory impairment. These results suggest a novel action site or mechanism for the attenuating effects of nociceptin and its metabolite, and the sequence of nociceptin (14-17) is a critical structure.
机译：Nociceptin与Nociceptin阿片肽（NOP）受体结合。我们报道了，尽管高剂量的伤害感受素会损害记忆功能，并且这些效应是通过NOP受体介导的，但低剂量的伤害感受素会减弱记忆力的损害，而这些衰减效应并非通过NOP受体介导的。甚至非常低剂量的伤害感受素都具有生物活性，并暗示了该肽的某个结合位点，但是尚未阐明这种减毒作用的机制。在本研究中，我们在降压型被动回避测试中研究了海马内注射（i.h.）伤害感受肽对U0126（一种MEK抑制剂）和Rp-cAMPS（一种PKA抑制剂）诱导的记忆障碍的影响。 U0126（2.63 nmol /小鼠，i.h。）损害了海马内的记忆形成和ERK2的训练依赖性磷酸化。共同给予伤害感受肽（10 fmol /小鼠）可显着减轻记忆障碍，但不能减弱U0126诱导的ERK2依赖于训练的磷酸化的抑制作用。另一方面，伤害感受肽不能减弱由Rp-cAMPS引起的记忆障碍（0.448nmol /小鼠，i.h。）。 Nociceptin（1 fmol /小鼠）还减弱了NOP受体敲除小鼠中的U0126（5.26 nmol /小鼠）引起的记忆障碍。据报道，伤害感受肽在体内代谢成片段（1-13）和（14-17），其显示出药理活性而不影响NOP受体。我们的研究结果表明，伤害感受肽（14-17）（1 fmol /小鼠）也能减轻U0126-诱导的记忆障碍，而伤害感受肽（1-13）（0.1-10 fmol /小鼠）不能减轻记忆障碍。这些结果提示了伤害感受素及其代谢产物的衰减作用的新作用位点或机制，伤害感受素的序列（14-17）是关键结构。

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