Welman A D, Daya S
Department of Biochemistry, Rhodes University, Grahamstown, South Africa.
J Neurosci Res. 1990 May;26(1):115-9. doi: 10.1002/jnr.490260115.
An attempt was made to use the pineal gland as a model for the study of the primary mode of action of alpha-methyldopa, which is still unclear. Organ cultures of pineal glands from rats treated chronically with alpha-methyldopa showed enhanced conversion of radio-active serotonin to melatonin (aMT) as well as its precursor, N-acetyl-serotonin (aHT). This treatment was also found to raise serotonin-N-acetyltransferase (NAT) activity. These increases associated with alpha-methyldopa treatment were further enhanced by the beta-adrenergic agonist, isoproterenol, suggesting a supersensitivity-type effect occurring at the level of the beta-receptor. A subsequent binding study, however, showed a decrease in beta-receptor binding with exposure to alpha-methyldopa, providing mitigating evidence against the occurrence of a supersensitivity phenomenon. It is possible that a metabolite of alpha-methyldopa acts as an alpha 1 and beta-agonist, resulting in greater melatonin (aMT) and N-acetylserotonin (aHT) synthesis than by a beta-agonist, isoproterenol.
有人尝试将松果体用作研究α-甲基多巴主要作用方式的模型，其作用方式仍不清楚。用α-甲基多巴长期处理的大鼠松果体器官培养物显示，放射性血清素向褪黑素（aMT）及其前体N-乙酰血清素（aHT）的转化增强。还发现这种处理可提高血清素-N-乙酰转移酶（NAT）的活性。β-肾上腺素能激动剂异丙肾上腺素进一步增强了与α-甲基多巴处理相关的这些增加，提示在β受体水平发生了超敏型效应。然而，随后的结合研究显示，暴露于α-甲基多巴时β受体结合减少，这为超敏现象的发生提供了反证。α-甲基多巴的一种代谢产物可能作为α1和β激动剂起作用，导致比β激动剂异丙肾上腺素产生更多的褪黑素（aMT）和N-乙酰血清素（aHT）。
