Rossetti Z L, Silvia C P, Krajnc D, Neff N H, Hadjiconstantinou M
Department of Pharmacology, Ohio State University College of Medicine, Columbus 43210.
J Neurochem. 1990 Mar;54(3):787-91. doi: 10.1111/j.1471-4159.1990.tb02320.x.
Aromatic L-amino acid decarboxylase (AAAD) activity of rat retina increases when animals are placed in a lighted environment from the dark. The increase of activity can be inhibited by administering the selective dopamine D1 receptor agonist SKF 38393, but not the selective D2 agonist quinpirole, or apomorphine. Conversely, in the dark, enzyme activity can be enhanced by administering the selective D1 antagonist SCH 23390 or haloperidol, but not the selective D2 antagonist (-)-sulpiride. Furthermore, in animals exposed to room light for 3 h, the D1 agonist SKF 38393 reduced retinal AAAD activity, and this effect was prevented by prior administration of SCH 23390. In contrast, quinpirole had little or no effect when administered to animals in the light. Kinetic analysis indicated that the apparent Vmax for the enzyme increases with little change in the apparent Km for the substrate 3,4-dihydroxyphenylalanine or the cofactor pyridoxal-5'-phosphate. We suggest that dopamine released in the dark tonically occupies D1 receptors and suppresses AAAD activity. When the room light is turned on, D1 receptors are vacated and selective D1 agonists can either prevent the rise of AAAD or reverse light-enhanced AAAD activity.
当动物从黑暗环境转移到光照环境中时，大鼠视网膜的芳香族L-氨基酸脱羧酶（AAAD）活性会增加。给予选择性多巴胺D1受体激动剂SKF 38393可抑制活性的增加，但给予选择性D2激动剂喹吡罗或阿扑吗啡则无此作用。相反，在黑暗中，给予选择性D1拮抗剂SCH 23390或氟哌啶醇可增强酶活性，但给予选择性D2拮抗剂（-）-舒必利则无此作用。此外，在暴露于室内光照3小时的动物中，D1激动剂SKF 38393降低了视网膜AAAD活性，而预先给予SCH 23390可阻止这种作用。相比之下，在光照条件下给予动物喹吡罗几乎没有影响。动力学分析表明，该酶的表观Vmax增加，而底物3,4-二羟基苯丙氨酸或辅因子磷酸吡哆醛的表观Km变化不大。我们认为，黑暗中释放的多巴胺持续占据D1受体并抑制AAAD活性。当打开室内灯光时，D1受体空出，选择性D1激动剂可以阻止AAAD活性升高或逆转光照增强的AAAD活性。
