Fassini Aline, Scopinho América A, Resstel Leonardo B M, Corrêa Fernando M A
Department of Pharmacology of the School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Department of Pharmacology of the School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Neuropeptides. 2016 Jun;57:35-44. doi: 10.1016/j.npep.2016.02.006. Epub 2016 Feb 24.
Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) have structural homology with classic opioids, but constitute a distinct neurotransmitter system because they lack affinity for the opioid peptides and receptors. This neurotransmission is implicated in several physiologic processes, but the role played by NOP receptors during stress situations remains unclear. The acute restraint stress (RS) is a model of unavoidable stress, characterized by sustained increases in mean arterial pressure (MAP), heart rate (HR) and a drop in tail temperature. On another side, the prelimbic (PL) and infralimbic (IL) cortices, subdivisions of the medial prefrontal cortex (MPFC), are implicated in the modulation of functional responses caused by RS. Considering that, the objective of the present study was to investigate the involvement of PL and IL NOP receptors in the control of autonomic responses induced by RS. Bilateral microinjection of nociceptin (NOP agonist) into the PL reduced the cardiovascular responses evoked by RS. Bilateral microinjection of UPF-101 (NOP antagonist) into the PL potentiated the pressor and tachycardiac responses evoked by RS, in a dose-dependent manner. Local pretreatment with UPF-101 blocked the RS-evoked changes following nociceptin administration into the PL. None of these treatments affected the drop in tail temperature induced by RS. Otherwise, the administration of nociceptin or UPF-101 into the IL had no effect on RS-evoked autonomic changes. To investigate the peripheral mechanism involved in the increase in the RS-evoked cardiovascular responses induced by the blockade of PL NOP receptors, rats were intravenous pretreated with either homatropine or atenolol. The intravenous treatment with homatropine blunted the increase in the RS-evoked pressor and tachycardiac response induced by the PL treatment with UPF-101, while the intravenous treatment with atenolol did not affect the RS-evoked pressor and tachycardiac response induced by the PL treatment with UPF-101. In conclusion, our study shows an influence of the PL N/OFQ neurotransmission, but not the IL NOP receptors, in the control of cardiovascular responses observed during acute stress, by increasing cardiac parasympathetic activity.
痛敏肽/孤啡肽（N/OFQ）及其受体（NOP）与经典阿片类物质具有结构同源性，但它们构成了一个独特的神经递质系统，因为它们对阿片肽和受体缺乏亲和力。这种神经传递参与了多个生理过程，但NOP受体在应激情况下所起的作用仍不清楚。急性束缚应激（RS）是一种不可避免的应激模型，其特征是平均动脉压（MAP）、心率（HR）持续升高以及尾温下降。另一方面，内侧前额叶皮质（MPFC）的亚区前边缘（PL）皮质和下边缘（IL）皮质参与了由RS引起的功能反应的调节。鉴于此，本研究的目的是探讨PL和IL NOP受体在控制RS诱导的自主反应中的作用。向PL双侧微量注射痛敏肽（NOP激动剂）可降低RS诱发的心血管反应。向PL双侧微量注射UPF-101（NOP拮抗剂）以剂量依赖的方式增强了RS诱发的升压和心动过速反应。用UPF-101进行局部预处理可阻断向PL注射痛敏肽后RS诱发的变化。这些处理均未影响RS诱导的尾温下降。此外，向IL注射痛敏肽或UPF-101对RS诱发的自主变化没有影响。为了研究PL NOP受体阻断引起的RS诱发的心血管反应增加所涉及的外周机制，对大鼠进行了静脉注射后马托品或阿替洛尔预处理。静脉注射后马托品可减弱PL注射UPF-101所诱发的RS诱发的升压和心动过速反应的增加，而静脉注射阿替洛尔对PL注射UPF-101所诱发的RS诱发的升压和心动过速反应没有影响。总之，我们的研究表明，PL N/OFQ神经传递通过增加心脏副交感神经活动，对急性应激期间观察到的心血管反应具有影响，而IL NOP受体则没有这种影响。
