Cerrito F, Raiteri M
Eur J Pharmacol. 1980 Dec 19;68(4):465-70. doi: 10.1016/0014-2999(80)90421-5.
The synthesis of dopamine from labeled tyrosine (but not from labeled DOPA) in rat striatal synaptosomes was effectively inhibited by exogenous dopamine only when the amine was allowed to enter the nerve endings. In the presence of the uptake blocker nomifensine, extracellular dopamine was almost inactive. The evolution of 14CO2 from [14C]tyrosine was consistently higher when synaptosomes were 'incubated' in the presence of nomifensine than in its absence. This effect disappeared when synaptosomes were 'superfused' with labeled tyrosine (with or without nomifensine) in conditions in which dopamine reuptake cannot occur. The monoaminoxidase inhibitor pargyline inhibited 14CO2 evolution from [14C]tyrosine. However, the effect was almost abolished if dopamine reuptake was prevented (by nomifensine or in superfusion). Our results suggest that dopaminergic nerve endings do not possess autoreceptors controlling dopamine synthesis. In the present paper it is proposed that the regulation of dopamine synthesis occurs through inhibition of tyrosine hydroxylase, according to the classical and end-product concept; however, the function of 'end-product' would be primarily exerted by the amine newly taken up by the nerve terminals.
仅当胺类物质能够进入神经末梢时，外源性多巴胺才能有效抑制大鼠纹状体突触小体中由标记酪氨酸（而非标记多巴）合成多巴胺的过程。在存在摄取阻滞剂诺米芬辛的情况下，细胞外多巴胺几乎没有活性。当突触小体在有诺米芬辛存在的情况下“孵育”时，[14C]酪氨酸生成14CO2的量始终高于无诺米芬辛时。当突触小体在多巴胺再摄取无法发生的条件下用标记酪氨酸（有无诺米芬辛）“灌流”时，这种效应消失。单胺氧化酶抑制剂帕吉林抑制[14C]酪氨酸生成14CO2。然而，如果阻止多巴胺再摄取（通过诺米芬辛或在灌流条件下），该效应几乎完全消失。我们的结果表明，多巴胺能神经末梢不具有控制多巴胺合成的自身受体。在本文中，根据经典的终产物概念，提出多巴胺合成的调节是通过抑制酪氨酸羟化酶来实现的；然而，“终产物”的功能主要由神经末梢新摄取的胺类物质发挥。
