Mustanoja S M, Hätönen T, Johansson-Alila A, Laakso M L
Department of Physiology, Institute of Biomedicine, University of Helsinki, Finland.
Eur J Pharmacol. 1997 May 20;326(2-3):229-36. doi: 10.1016/s0014-2999(97)85418-0.
This study was done to clarify the role of alpha2-adrenoceptors in the regulation of pineal melatonin synthesis. A selective alpha2-adrenoceptor agonist, medetomidine, and antagonist, atipamezole, were injected subcutaneously into rats and their pineal melatonin contents were measured by radioimmunoassay. Medetomidine (120 microg/kg) suppressed melatonin at night to a similar extent during the rising and descending phase of melatonin synthesis, but it did not affect the daytime level. A dose of 12 microg/kg was ineffective; doses of 30-180 microg/kg suppressed nocturnal melatonin levels close to the daytime levels. Significant suppression was reached within 15 min and the effect started to fade 3 h after the injection (120 microg/kg). At midday, medetomidine did not inhibit isoproterenol-stimulated synthesis of melatonin. Atipamezole (0.4 or 1.2 mg/kg) had no effect alone, but it counteracted the medetomidine-induced suppression. The effects of alpha2-adrenoceptor ligands on melatonin synthesis depend on the time of day and/or on the activity of the pineal sympathetic nerves.
本研究旨在阐明α2-肾上腺素能受体在松果体褪黑素合成调节中的作用。将选择性α2-肾上腺素能受体激动剂美托咪定和拮抗剂阿替美唑皮下注射到大鼠体内，并用放射免疫分析法测定其松果体褪黑素含量。美托咪定（120微克/千克）在褪黑素合成的上升和下降阶段，夜间对褪黑素的抑制程度相似，但不影响白天的水平。12微克/千克的剂量无效；30-180微克/千克的剂量可将夜间褪黑素水平抑制至接近白天水平。注射后15分钟内达到显著抑制，注射后3小时（120微克/千克）效果开始消退。中午时，美托咪定不抑制异丙肾上腺素刺激的褪黑素合成。阿替美唑（0.4或1.2毫克/千克）单独使用无作用，但可抵消美托咪定引起的抑制作用。α2-肾上腺素能受体配体对褪黑素合成的影响取决于一天中的时间和/或松果体交感神经的活动。
