Venero J L, Machado A, Cano J
Departamento de Bioquímica, Facultad de Farmacia, Universidad de Sevilla, Spain.
J Neurochem. 1991 Jun;56(6):1940-8. doi: 10.1111/j.1471-4159.1991.tb03451.x.
Turnover of dopamine (DA), serotonin [5-hydroxytryptamine (5-HT)], and their metabolites has been measured in adult and aged rats. Turnover rates of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxy-3-indoleacetic acid (5-HIAA) have been assayed from the disappearance rates after blocking by pargyline inhibition of monoamine oxidase (MAO) and from the accumulation rates by probenecid inhibition of the probenecid-sensitive transport system. DA and 5-HT turnover rates have been measured as accumulation rates of 3,4-dihydroxyphenylalanine and 5-hydroxytryptophan, respectively, after central decarboxylase inhibition by 3-hydroxybenzylhydrazine (NSD-1015) and as accumulation rates of DA and 5-HT after pargyline inhibition of MAO. The DA turnover rate after NSD-1015 was 23.9% lower in aged rats than in adults, whereas after pargyline there was no significant difference between the two age groups. The HVA fractional rate constant and turnover after pargyline were lower in aged rats than in adults, and HVA turnover after probenecid was higher in aged rats than in adults. The DOPAC-HVA pathway seems to be reinforced at the expense of DOPAC conjugation. In aged and adult rats whose 5-HT steady-state levels were not statistically different, the 5-HT turnover rate after pargyline and NSD-1015 treatment was lower in aged rats than in adults. An increase of 5-HIAA levels after pargyline and probenecid treatment in aged rats could be due to the handling stress.
已对成年和老年大鼠体内多巴胺(DA)、血清素[5-羟色胺(5-HT)]及其代谢产物的周转率进行了测定。通过使用帕吉林抑制单胺氧化酶(MAO)后测定3,4-二羟基苯乙酸(DOPAC)、高香草酸(HVA)和5-羟基-3-吲哚乙酸(5-HIAA)的消失率,以及使用丙磺舒抑制丙磺舒敏感转运系统后测定其积累率,来分析这些物质的周转率。DA和5-HT的周转率分别通过3-羟基苄基肼(NSD-1015)抑制中枢脱羧酶后3,4-二羟基苯丙氨酸和5-羟色氨酸的积累率来测定,以及通过帕吉林抑制MAO后DA和5-HT的积累率来测定。NSD-1015处理后,老年大鼠的DA周转率比成年大鼠低23.9%,而帕吉林处理后,两个年龄组之间没有显著差异。老年大鼠帕吉林处理后的HVA分数速率常数和周转率低于成年大鼠,丙磺舒处理后老年大鼠的HVA周转率高于成年大鼠。DOPAC-HVA途径似乎以DOPAC结合为代价得到加强。在5-HT稳态水平无统计学差异的老年和成年大鼠中,帕吉林和NSD-1015处理后老年大鼠的5-HT周转率低于成年大鼠。老年大鼠帕吉林和丙磺舒处理后5-HIAA水平升高可能是由于处理应激所致。