Kapoor V, Chalmers J
Department of Medicine, Flinders Medical Centre, Bedford Park, South Australia.
Eur J Pharmacol. 1989 May 30;164(3):531-8. doi: 10.1016/0014-2999(89)90261-6.
Blood pressure (BP), hypothalamic tissue concentrations and the in vivo overflow of endogenous and alpha-methylated catecholamines were measured in urethane anaesthetised rats after alpha-methylDOPA (mDOPA) administration (200 mg/kg i.p.). Four hours after mDOPA, BP fell to its lowest value, 60% of control, and slowly returned towards control levels by 24 h. This was closely correlated with the evoked overflow of alpha-methylnoradrenaline (mNA, r = 0.9) and noradrenaline (NA, r = 0.7) but not dopamine (DA) or alpha-methyldopamine (mDA). However, the tissue content of mNA rose much more gradually and was not maximal until after 12 h while mDA content followed the development of the hypotension. The results provide direct evidence for a false transmitter role for mNA in the brain, and suggest that the release of newly synthesised mNA is responsible for the hypotensive effect of mDOPA. Differences in the time course of overflow and storage of NA and mNA suggest the presence of separate transmitter storage and releasable pools.
在给乌拉坦麻醉的大鼠腹腔注射α-甲基多巴（mDOPA，200mg/kg）后，测量其血压（BP）、下丘脑组织中内源性和α-甲基化儿茶酚胺的浓度以及体内溢出量。注射mDOPA 4小时后，血压降至最低值，为对照值的60%，并在24小时内缓慢恢复至对照水平。这与α-甲基去甲肾上腺素（mNA，r = 0.9）和去甲肾上腺素（NA，r = 0.7）的诱发溢出密切相关，但与多巴胺（DA）或α-甲基多巴胺（mDA）无关。然而，mNA的组织含量上升更为缓慢，直到12小时后才达到最大值，而mDA含量则随低血压的发展而变化。这些结果为mNA在大脑中作为假递质的作用提供了直接证据，并表明新合成的mNA的释放是mDOPA降压作用的原因。NA和mNA在溢出和储存时间进程上的差异表明存在单独的递质储存和可释放池。
