Department of Pharmacology and Therapeutics, State University of Maringá (UEM), Maringá, PR, Brazil.
Department of Pharmacology and Therapeutics, State University of Maringá (UEM), Maringá, PR, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):493-498. doi: 10.1016/j.pnpbp.2017.08.003. Epub 2017 Aug 7.
Reported results have shown that the pentapeptide opiorphin inhibits oligopeptidases that degrade brain neuropeptides, and has analgesic and antidepressant effects in experimental animals, without either tolerance or dependency after chronic administration. In a previous study we showed that opiorphin has a panicolytic-like effect in the dorsal periaqueductal gray (dPAG) electrical stimulation test (EST), mediated by the μ-opioid receptor (MOR). This study further analyzes the mechanism of opiorphin panicolytic action, using the EST and drug injection inside the dPAG. The obtained results showed that blockade of the 5-HT receptors with WAY-100635 did not change the escape-impairing effect of opiorphin, and combined injection of sub-effective doses of opiorphin and the 5-HT-agonist 8-OH-DPAT did not have a significant anti-escape effect. In contrast, the anti-escape effect of opiorphin was antagonized by pretreatment with the kinin B2 receptor blocker HOE-140, and association of sub-effective doses of opiorphin and bradykinin caused a significant anti-escape effect. The anti-escape effect of bradykinin was not affected by previous administration of WAY-100635. Therefore, the anti-escape effect of opiorphin in the dPAG seems to be mediated by endogenous bradykinin, acting on kinin B2 receptors, which previous results have shown to interact synergistically with MOR in the dPAG to restrain escape in two animal models of panic. Chemical compounds: Opiorphin (PubChem CID: 25195667); WAY100635 maleate salt (PubChem CID: 11957721); 8-OH-DPAT hydrobromide (PubChem CID: 6917794); Bradykinin (PubChem CID: 439201); HOE-140 (Icatibant) (PubChem CID: 6918173).
研究结果表明，五肽脑啡肽可抑制降解脑神经肽的寡肽酶，在实验动物中具有镇痛和抗抑郁作用，且在慢性给药后无耐受或依赖。在之前的研究中，我们表明脑啡肽在背侧导水管周围灰质（dPAG）电刺激测试（EST）中具有恐慌样作用，这是由μ阿片受体（MOR）介导的。本研究进一步分析了脑啡肽恐慌样作用的机制，使用 EST 和 dPAG 内药物注射。获得的结果表明，用 WAY-100635 阻断 5-HT 受体不会改变脑啡肽的逃避损伤作用，并且脑啡肽和 5-HT 激动剂 8-OH-DPAT 的亚有效剂量联合注射没有显著的抗逃避作用。相反，脑啡肽的抗逃避作用被缓激肽 B2 受体阻滞剂 HOE-140 的预处理所拮抗，而亚有效剂量的脑啡肽和缓激肽的联合注射引起了显著的抗逃避作用。缓激肽的抗逃避作用不受 WAY-100635 预先给药的影响。因此，dPAG 中脑啡肽的抗逃避作用似乎是由内源性缓激肽介导的，作用于缓激肽 B2 受体，先前的结果表明，缓激肽 B2 受体与 dPAG 中的 MOR 协同作用，在两种恐慌动物模型中抑制逃避。
脑啡肽（PubChem CID：25195667）；马来酸 WAY-100635（PubChem CID：11957721）；8-OH-DPAT 氢溴酸盐（PubChem CID：6917794）；缓激肽（PubChem CID：439201）；HOE-140（Icatibant）（PubChem CID：6918173）。
