Substance P is involved in terminating the hypothalamo- pituitary-adrenal axis response to acute stress through centrally located neurokinin-1 receptors.
Substance P is involved in terminating the hypothalamo- pituitary-adrenal axis response to acute stress through centrally located neurokinin-1 receptors.
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DOI：
10.3109/10253890009001125
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发表时间：
2000-05-01
期刊：
影响因子：
--
通讯作者：
Harbuz, M S
中科院分区：
文献类型：
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作者：
Jessop, D S;Renshaw, D;Harbuz, M S
神经激肽P物质（SP）以前已被证明抑制基础下丘脑-垂体-肾上腺（HPA）轴的活动。本研究旨在探讨中枢注射特异性神经激肽1受体拮抗剂RP 67580对急性束缚应激下丘脑-垂体-肾上腺轴反应的影响。在注射RP 67580的非束缚大鼠中，与注射溶剂的大鼠相比，血浆ACTH和皮质酮水平在30和60 min时升高，但在4 h时溶剂组和RP 67580组之间无差异。在约束大鼠注射车辆，血浆ACTH和皮质酮水平显着升高，在30分钟和60分钟后开始的压力，但已恢复到基础水平，在4小时。在用RP 67580 icv注射的束缚大鼠中，血浆皮质酮和ACTH水平在30 min和60 min时显著升高，与束缚应激溶媒注射组相比无显著差异。然而，在RP 67580注射组中，与束缚应激溶剂注射组相比，皮质酮和ACTH水平在束缚开始后4小时仍显著升高。与仅注射溶剂的应激组相比，注射RP 67580后4 h应激组下丘脑室旁核小细胞亚群中促肾上腺皮质激素释放因子mRNA水平和垂体前叶中POMC mRNA水平显著升高。这些数据表明，内源性SP不会抑制HPA轴对束缚应激反应的初始幅度，但确实通过中枢水平的神经激肽-1受体发挥作用，以减少对应激反应的持续时间。这表明，SP可能是一个重要的中枢代理控制急性和慢性应激之间的过渡。
The neurokinin substance P (SP) has been previously shown to inhibit basal hypothalamo-pituitary-adrenal (HPA) axis activity. This study was designed to investigate the effects of central injection of the specific neurokinin-1 receptor antagonist RP67580 on the HPA axis response to acute restraint stress. In non-restrained rats injected with RP67580, plasma ACTH and corticosterone levels were elevated at 30 and 60 min compared to rats injected with vehicle, but there were no differences between vehicle and RP67580 groups at 4h. In restrained rats injected with vehicle, plasma ACTH and corticosterone levels were significantly elevated at 30 min and 60 min following initiation of the stress but had returned to basal levels at 4h. In restrained rats injected icv with RP67580, plasma corticosterone and ACTH levels were significantly elevated at 30 min and 60 min, with no significant differences compared to the restraint stressed vehicle-injected group. However, in the RP67580-injected group, corticosterone and ACTH levels remained significantly elevated at 4h following onset of restraint compared to those in the restraint stressed vehicle-injected group. Corticotrophin-releasing factor mRNA levels in the parvocellular subdivision of the paraventricular nucleus of the hypothalamus and POMC mRNA levels in the anterior pituitary were significantly increased in the stressed group 4h following injection with RP67580 compared to the stressed group injected with vehicle alone. These data show that endogenous SP does not inhibit the initial magnitude of the HPA axis response to restraint stress, but does act through neurokinin-1 receptors at a central level to reduce the duration of the response to stress. This suggests that SP may be an important central agent controlling the transition between acute and chronic stress.