Pfeffer R I, Mosimann W F, Weiner N
J Pharmacol Exp Ther. 1975 May;193(2):533-48.
During the first several hours after administration of reserpine, tyrosine hydroxylase activity in rat adrenal slices and in isolated intact vasa deferentia of mice and rats is profoundly reduced, although no effect on enzyme activity in isolated fortified homogenates of these tissues is demonstrable. This effect, observed only in intact preparations, is competitively antagonized by addition to the medium of the synthetic pterin cofactor, 6,7-dimethyltetrahydropterin (DMPH4). Kinetic analysis of the effect of acute reserpine treatment on tyrosine hydroxylase activity in these isolated, intact tissues indicates that the Km for the pterin cofactor is increased but the Vmax is not altered. The results indicate that reserpine produces its inhibition of tyrosine hydroxylase by preventing catecholamine storage and causing elevated levels of free intraneuronal norepinephrine. The catecholamine inhibits the enzyme in a manner which is competitive with the pterin cofactor. After more chronic reserpine treatment, when catecholamine stores are severly depleted, this inhibition of tyrosine hydroxylase activity in intact tissues is no longer apparent. After 3 days of treatment, increased levels of tyrosine hydroxylase are demonstrable in the adrenal glands of rats but not in the vass deferentia of either mice or rats. The increased enzyme levels in the adrenal gland are presumably due to increased enzyme formation.
利血平给药后的最初几个小时内，大鼠肾上腺切片以及小鼠和大鼠分离的完整输精管中的酪氨酸羟化酶活性会显著降低，尽管在这些组织的分离强化匀浆中未显示对酶活性有影响。这种仅在完整制剂中观察到的效应，可通过在培养基中添加合成蝶呤辅因子6,7-二甲基四氢蝶呤（DMPH4）而受到竞争性拮抗。对急性利血平处理对这些分离的完整组织中酪氨酸羟化酶活性的影响进行动力学分析表明，蝶呤辅因子的Km增加，但Vmax未改变。结果表明，利血平通过阻止儿茶酚胺储存并导致神经元内游离去甲肾上腺素水平升高来抑制酪氨酸羟化酶。儿茶酚胺以与蝶呤辅因子竞争的方式抑制该酶。经过更长期的利血平处理后，当儿茶酚胺储存严重耗尽时，完整组织中酪氨酸羟化酶活性的这种抑制作用不再明显。处理3天后，大鼠肾上腺中酪氨酸羟化酶水平升高，但小鼠或大鼠的输精管中未升高。肾上腺中酶水平的升高可能是由于酶形成增加所致。
