Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China.
Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, China.
Can J Physiol Pharmacol. 2021 Oct;99(10):1057-1068. doi: 10.1139/cjpp-2020-0668. Epub 2021 Sep 7.
G (1-5)-NH, G (1-7)-NH, and G (1-9) are the active fragments of ghrelin. The aim of this study was to investigate the antinociceptive effects, their ability to cross the blood-brain barrier, and the receptor mechanism(s) of these fragments using the tail withdrawal test in male Kunming mice. The antinociceptive effects of these fragments (2, 6, 20, and 60 nmol/mouse) were tested at 5, 10, 20, 30, 40, 50, and 60 min after intravenous (i.v.) injection. These fragments induced dose- and time-related antinociceptive effects relative to saline. Using the near infrared fluorescence imaging experiments, our results showed that these fragments could cross the brain-blood barrier and enter the brain. The antinociceptive effects of these fragments were completely antagonized by naloxone (intracerebroventricular, i.c.v.); however, naloxone methiodide (intraperitoneal, i.p.), which is the peripheral restricted opioid receptor antagonist, did not antagonize these antinociceptive effects. Furthermore, the GHS-R1α antagonist [D-Lys]-GHRP-6 (i.c.v.) completely antagonized these antinociceptive effects, too. These results suggested that these fragments induced antinociceptive effects through central opioid receptors and GHS-R1α. In conclusion, our studies indicated that these active fragments of ghrelin could cross the brain-blood barrier and enter the brain and induce antinociceptive effects through central opioid receptors and GHS-R1α after intravenous injection.
G (1-5)-NH、G (1-7)-NH 和 G (1-9) 是 ghrelin 的活性片段。本研究旨在通过昆明雄性小鼠的尾部退缩试验，研究这些片段的镇痛作用、穿过血脑屏障的能力以及受体机制。在静脉注射后 5、10、20、30、40、50 和 60 分钟，测试这些片段（2、6、20 和 60 nmol/只）的镇痛作用。这些片段表现出剂量和时间相关的镇痛作用，与生理盐水相比。通过近红外荧光成像实验，我们的结果表明这些片段可以穿过血脑屏障进入大脑。这些片段的镇痛作用被纳洛酮（脑室内，i.c.v.）完全拮抗；然而，纳洛酮甲碘化物（腹腔内，i.p.），一种外周受限的阿片受体拮抗剂，并没有拮抗这些镇痛作用。此外，GHS-R1α 拮抗剂 [D-Lys]-GHRP-6（脑室内，i.c.v.）也完全拮抗了这些镇痛作用。这些结果表明这些片段通过中枢阿片受体和 GHS-R1α 诱导镇痛作用。总之，我们的研究表明，这些 ghrelin 的活性片段可以穿过血脑屏障进入大脑，并在静脉注射后通过中枢阿片受体和 GHS-R1α 诱导镇痛作用。
