Mustanoja S M, Hätönen T, Alila-Johansson A, Laakso M L
Department of Physiology, Institute of Biomedical, University of Helsinki, Finland.
Neuroscience. 1999;92(3):967-73. doi: 10.1016/s0306-4522(99)00057-3.
This study was carried out to clarify the role of alpha2-adrenoceptors in the regulation of pineal melatonin synthesis. Medetomidine, a selective alpha2-adrenoceptor agonist, was previously found to be a potent suppressor of nocturnal melatonin levels in rats. Medetomidine and alpha2-adrenoceptor antagonists atipamezole and yohimbine were injected into rats in different conditions, and their pineal melatonin contents were measured by radioimmunoassay. Experiment 1: Blocking the alpha2-adrenoceptors and possible non-adrenergic binding sites with atipamezole did not counteract the light-induced suppression of nocturnal melatonin. These receptors are, thus, not essential for the suppression of melatonin by light. Experiment 2: Blocking the alpha2-adrenoceptors with atipamezole or yohimbine did not sensitize the pineal melatonin synthesis to daytime darkness in the light/dark-entrained rats. The binding sites are not involved in keeping the daytime melatonin levels low, even in darkness. Experiment 3: The rats were sensitized to daytime darkness by keeping them for seven days in constant light. The dark-elicited melatonin rise was suppressed by a lower dose of medetomidine than the normal nocturnal rise in light/dark-entrained rats, while atipamezole had no effect. The results showed that alpha2-adrenoceptor insufficiency is not involved in the constant light-induced pineal supersensitivity. In summary, the experiments indicated that the physiological regulation of melatonin synthesis by ambient lighting in rats does not depend on alpha2-adrenergic mechanisms.
本研究旨在阐明α2-肾上腺素能受体在调节松果体褪黑素合成中的作用。美托咪定是一种选择性α2-肾上腺素能受体激动剂，此前被发现是大鼠夜间褪黑素水平的强效抑制剂。在不同条件下将美托咪定以及α2-肾上腺素能受体拮抗剂阿替美唑和育亨宾注射到大鼠体内，并用放射免疫分析法测定其松果体褪黑素含量。实验1：用阿替美唑阻断α2-肾上腺素能受体和可能的非肾上腺素能结合位点并不能抵消光诱导的夜间褪黑素抑制作用。因此，这些受体对于光抑制褪黑素并非必不可少。实验2：在明暗交替饲养的大鼠中，用阿替美唑或育亨宾阻断α2-肾上腺素能受体并不会使松果体褪黑素合成对白天黑暗敏感。即使在黑暗中，这些结合位点也不参与维持白天较低的褪黑素水平。实验3：通过将大鼠在持续光照下饲养7天使其对白天黑暗敏感。与明暗交替饲养的大鼠正常夜间升高相比，较低剂量的美托咪定即可抑制黑暗诱导的褪黑素升高，而阿替美唑则无作用。结果表明，α2-肾上腺素能受体功能不足与持续光照诱导的松果体超敏反应无关。总之，实验表明大鼠中环境光照对褪黑素合成的生理调节不依赖于α2-肾上腺素能机制。
