McQuade P S, Juorio A V
J Neurosci Res. 1983;10(2):127-34. doi: 10.1002/jnr.490100202.
Acid hydrolysis of mouse caudate homogenates results in a significantly increased concentration of para-hydroxyphenylacetic acid (p-HPAA). Thus p-HPAA appears to be significantly present as an acid-labile conjugate in the mouse caudate nucleus. Saline injection also increased the concentration of the acid metabolite of the tyramines. The subcutaneous injection of either meta-hydroxyphenylacetic acid (m-HPAA) or p-HPAA or both produced at 0.5 hr and 2.0 hr large increases in the mouse caudate nucleus concentrations of m- and/or p-HPAA. Similarly at 2.0 hr the injection of a combination of para- and meta-tyramine caused large increases in the acid metabolite concentrations. Probenecid, at a dose of 500 mg/kg, increased striatal p-HPAA and m-HPAA concentrations. Probenecid, injection prior to the administration of p-HPAA and m-HPAA, did not reduce the increased concentrations of these two acid metabolites previously observed after the administration of the acid metabolites alone. It thus appears that p-HPAA and m-HPAA are transported from the brain by a probenecid-sensitive mechanism, but in the presence of high blood concentrations, p-HPAA and m-HPAA may enter the brain by a mechanism that is not affected by probenecid.
小鼠尾状核匀浆的酸水解导致对羟基苯乙酸(p-HPAA)浓度显著增加。因此,p-HPAA似乎以酸不稳定结合物的形式大量存在于小鼠尾状核中。注射生理盐水也会增加酪胺酸代谢产物的浓度。皮下注射间羟基苯乙酸(m-HPAA)或p-HPAA或两者,在0.5小时和2.0小时时会使小鼠尾状核中m-HPAA和/或p-HPAA的浓度大幅增加。同样,在2.0小时时,注射对酪胺和间酪胺的组合会使酸代谢产物浓度大幅增加。剂量为500mg/kg的丙磺舒会增加纹状体中p-HPAA和m-HPAA的浓度。在注射p-HPAA和m-HPAA之前注射丙磺舒,并不会降低之前单独注射酸代谢产物后观察到的这两种酸代谢产物增加的浓度。因此,似乎p-HPAA和m-HPAA是通过一种对丙磺舒敏感的机制从大脑中转运出来的,但在高血药浓度的情况下,p-HPAA和m-HPAA可能通过一种不受丙磺舒影响的机制进入大脑。