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纳洛酮对环甘氨酰脯氨酸诱导的小鼠唾液分泌减少和颌下腺成分的恢复作用。

Restoration of Cyclo-Gly-Pro-induced salivary hyposecretion and submandibular composition by naloxone in mice.

机构信息

Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil.

Optics and Materials Group, Optma, Federal University of Alagoas, Maceio, Alagoas, Brazil.

出版信息

PLoS One. 2020 Mar 10;15(3):e0229761. doi: 10.1371/journal.pone.0229761. eCollection 2020.

DOI:10.1371/journal.pone.0229761
PMID:32155179
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7064257/
Abstract

Cyclo-Gly-Pro (CGP) attenuates nociception, however its effects on salivary glands remain unclear. In this study, we investigated the acute effects of CGP on salivary flow and composition, and on the submandibular gland composition, compared with morphine. Besides, we characterized the effects of naloxone (a non-selective opioid receptor antagonist) on CGP- and morphine-induced salivary and glandular alterations in mice. After that, in silico analyses were performed to predict the interaction between CGP and opioid receptors. Morphine and CGP significantly reduced salivary flow and total protein concentration of saliva and naloxone restored them to the physiological levels. Morphine and CGP also reduced several infrared vibrational modes (Amide I, 1687-1594cm-1; Amide II, 1594-1494cm-1; CH2/CH3, 1488-1433cm-1; C = O, 1432-1365cm-1; PO2 asymmetric, 1290-1185cm-1; PO2 symmetric, 1135-999cm-1) and naloxone reverted these alterations. The in silico docking analysis demonstrated the interaction of polar contacts between the CGP and opioid receptor Cys219 residue. Altogether, we showed that salivary hypofunction and glandular changes elicited by CGP may occur through opioid receptor suggesting that the blockage of opioid receptors in superior cervical and submandibular ganglions may be a possible strategy to restore salivary secretion while maintaining antinociceptive action due its effects on the central nervous system.

摘要

环甘氨酰脯氨酸（CGP）可减轻痛觉，但它对唾液腺的影响尚不清楚。在这项研究中，我们研究了 CGP 对唾液流量和成分以及颌下腺组成的急性影响，并与吗啡进行了比较。此外，我们还研究了纳洛酮（一种非选择性阿片受体拮抗剂）对 CGP 和吗啡引起的小鼠唾液腺和腺体改变的影响。之后，我们进行了计算机模拟分析，以预测 CGP 与阿片受体的相互作用。吗啡和 CGP 显著减少唾液流量和唾液中的总蛋白浓度，纳洛酮将其恢复到生理水平。吗啡和 CGP 还减少了几个红外振动模式（酰胺 I，1687-1594cm-1；酰胺 II，1594-1494cm-1；CH2/CH3，1488-1433cm-1；C=O，1432-1365cm-1；PO2 不对称，1290-1185cm-1；PO2 对称，1135-999cm-1），纳洛酮将这些改变逆转。计算机对接分析表明，CGP 与阿片受体 Cys219 残基之间存在极性接触相互作用。总的来说，我们表明 CGP 引起的唾液分泌减少和腺体变化可能通过阿片受体发生，这表明阻断颈上神经节和颌下神经节中的阿片受体可能是恢复唾液分泌的一种可行策略，同时由于其对中枢神经系统的影响，保持抗伤害作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea1/7064257/8c234b01e3bc/pone.0229761.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea1/7064257/8c234b01e3bc/pone.0229761.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea1/7064257/e9bf47b3d18c/pone.0229761.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea1/7064257/ae62e96121a7/pone.0229761.g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea1/7064257/8c234b01e3bc/pone.0229761.g006.jpg

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