Fuller R W, Hemrick-Luecke S K, Perry K W
J Pharmacol Exp Ther. 1982 Oct;223(1):84-9.
L-Dopa injected at 200 mg/kg i.p. into rats caused a slight reduction in hypothalamic concentration of epinephrine and completely prevented the accumulation of epinephrine after monoamine oxidase inhibition. The lowering of epinephrine concentration was greater with L-dopa than with D-dopa, was dose-related over a dosage range of 50 to 200 mg/kg of L-dopa and was not prevented by a dopamine receptor antagonist. Hypothalamic norepinephrine N-methyltransferase activity measured in vitro was not altered in rats treated with L-dopa. L-Dopa injection decreased S-adenosylmethionine (SAMe) concentration and increased S-adenosylhomocysteine (SAH) concentration in hypothalamus, probably a result of extensive O-methylation of L-dopa and its metabolites. The decrease in SAMe and epinephrine concentration and the increase in SAH concentration occurred at lower doses of L-dopa in carbidopa-pretreated rats than in control rats. Norepinephrine N-Methyl-transferase activity assayed in vitro was markedly inhibited by SAH; the inhibition was competitive with SAMe as the variable substrate and the Ki for SAH was 1.9 x 10(-5) M. Increasing the SAH/SAMe ratio in in vitro experiments sharply reduced norepinephrine N-methyltransferase activity. The apparent inhibition of hypothalamic epinephrine synthesis in vivo after L-dopa injection is suggested to be a consequence of the increased SAH/SAMe ratio.
腹腔注射200mg/kg左旋多巴可使大鼠下丘脑肾上腺素浓度略有降低，并能完全阻止单胺氧化酶抑制后肾上腺素的蓄积。左旋多巴降低肾上腺素浓度的作用比右旋多巴更强，在50至200mg/kg左旋多巴的剂量范围内呈剂量相关，且不受多巴胺受体拮抗剂的影响。体外测定的左旋多巴处理大鼠下丘脑去甲肾上腺素N-甲基转移酶活性未发生改变。注射左旋多巴可降低下丘脑S-腺苷甲硫氨酸（SAMe）浓度并升高S-腺苷同型半胱氨酸（SAH）浓度，这可能是左旋多巴及其代谢产物广泛O-甲基化的结果。与对照大鼠相比，在预先用卡比多巴处理的大鼠中，较低剂量的左旋多巴即可导致SAMe和肾上腺素浓度降低以及SAH浓度升高。体外测定时，SAH可显著抑制去甲肾上腺素N-甲基转移酶活性；该抑制作用以SAMe作为可变底物时具有竞争性，SAH的Ki为1.9×10⁻⁵M。在体外实验中增加SAH/SAMe比值可显著降低去甲肾上腺素N-甲基转移酶活性。提示注射左旋多巴后体内下丘脑肾上腺素合成的明显抑制是SAH/SAMe比值升高的结果。
