Rossi Grace C, Pellegrino Michael, Shane Randi, Abbadie Catherine A, Dustman Jessica, Jimenez Charles, Bodnar Richard J, Pasternak Gavril W, Allen Richard G
Long Island University, Brookville, New York 11548, USA.
J Pharmacol Exp Ther. 2002 Jan;300(1):257-64. doi: 10.1124/jpet.300.1.257.
Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the orphan receptor-like/kappa(3)-like opioid receptor clone, produces a variety of behavioral responses, including those associated with pronociception and antinociception. The OFQ/N precursor rattus-proOFQ (rppOFQ/N) contains several paired basic amino acids, which raises the possibility that post-translational processing can be responsible for the production of a number of additional biologically active peptide fragments. One of these putative peptides, rppOFQ/N (rppOFQ/N(154-181)), was examined for antinociceptive and pronociceptive processes in four brain sites involved in pain inhibition: the ventrolateral periaqueductal gray (vlPAG), the amygdala, the locus coeruleus (LC), and the rostroventromedial medulla (RVM). Endogenous rppOFQ/N(154-181) was identified in each region. rppOFQ/N(154-181) produced a dose-dependent antinociception in all four sites using the tailflick assay. Injections into misplaced cannula sites failed to exert effects. Antinociception in the four sites differed in their response to the opioid antagonist naloxone. Naloxone pretreatment completely blocked rppOFQ/N(154-181)-induced antinociception in the vlPAG and the amygdala, but not in the LC or RVM. In contrast rppOFQ/N(154-181) was hyperalgesic in the LC and RVM, but not in the vlPAG or amygdala. rppOFQ/N(154-181) also was compared with either its N-terminal 17-amino acid peptide (rppOFQ/N(154-170), also known as OFQ2) or its 8-amino acid C-terminal fragment (rppOFQ/N(174-181)). Although both rppOFQ/N(154-181) and rppOFQ/N(154-170) produced antinociception, the latter was less effective because the C-terminal fragment was inactive. Thus, rppOFQ/N(154-181) has complex antinociceptive and pronociceptive actions within the brain, and the pharmacological specificity of its actions differs among supraspinal sites.
孤啡肽/痛敏肽（OFQ/N）是孤儿受体样/κ（3）样阿片受体克隆的内源性配体，可产生多种行为反应，包括那些与促伤害感受和抗伤害感受相关的反应。OFQ/N前体大鼠-proOFQ（rppOFQ/N）包含几个成对的碱性氨基酸，这增加了翻译后加工可能负责产生许多额外生物活性肽片段的可能性。其中一种假定的肽，rppOFQ/N（rppOFQ/N(154 - 181)），在参与疼痛抑制的四个脑区：腹外侧导水管周围灰质（vlPAG）、杏仁核、蓝斑（LC）和延髓头端腹内侧区（RVM）中，被检测其抗伤害感受和促伤害感受过程。在每个区域都鉴定出了内源性rppOFQ/N(154 - 181)。使用甩尾试验，rppOFQ/N(154 - 181)在所有四个脑区均产生剂量依赖性的抗伤害感受作用。注射到错位的套管部位则没有效果。四个脑区的抗伤害感受对阿片类拮抗剂纳洛酮的反应不同。纳洛酮预处理完全阻断了rppOFQ/N(154 - 181)在vlPAG和杏仁核中诱导的抗伤害感受，但在LC或RVM中则没有。相反，rppOFQ/N(154 - 181)在LC和RVM中具有痛觉过敏作用，但在vlPAG或杏仁核中则没有。rppOFQ/N(154 - 181)还与它的N端17个氨基酸的肽（rppOFQ/N(154 - 170)，也称为OFQ2）或其8个氨基酸的C端片段（rppOFQ/N(174 - 181)）进行了比较。尽管rppOFQ/N(154 - 181)和rppOFQ/N(154 - 170)都产生抗伤害感受作用，但后者效果较差，因为C端片段没有活性。因此，rppOFQ/N(154 - 181)在脑内具有复杂的抗伤害感受和促伤害感受作用，并且其作用的药理学特异性在脊髓上部位之间有所不同。
