Hurd Y L, Ungerstedt U
Karolinska Institute, Pharmacology Department, Stockholm, Sweden.
Eur J Pharmacol. 1989 Jul 18;166(2):261-9. doi: 10.1016/0014-2999(89)90067-8.
The present in vivo microdialysis study examined the role of vesicular- and carrier-mediated mechanisms underlying dopamine (DA) release, uptake and metabolism in halothane-anaesthetized rats. Omission of calcium (Ca2+) from the dialysis perfusing medium, thereby reducing the concentration of Ca2+ in the striatal microenvironment necessary for vesicular DA release, attenuated the elevation of DA normally induced by the potent DA uptake inhibitors, nomifensine and Lu 19-005. Consistent with the results of in vitro studies, amphetamine release DA in a Ca2+-independent manner. The release of DA induced by amphetamine could be effectively blocked by nomifensine and Lu 19-005, demonstrating that the in vivo movement of amines occurred via a transport carried-mediated mechanism. Additionally, the inhibition of DA metabolism produced by amphetamine could be reversed or blocked by prior or delayed treatment with DA uptake inhibitors. The results support a bidirectional in vivo capability of the amine transport carrier.
目前的体内微透析研究考察了在氟烷麻醉大鼠中，囊泡介导和载体介导机制在多巴胺（DA）释放、摄取及代谢过程中的作用。从透析灌注培养基中去除钙（Ca2+），从而降低囊泡DA释放所需的纹状体微环境中的Ca2+浓度，减弱了强效DA摄取抑制剂诺米芬辛和Lu 19-005通常诱导的DA升高。与体外研究结果一致，苯丙胺以不依赖Ca2+的方式释放DA。苯丙胺诱导的DA释放可被诺米芬辛和Lu 19-005有效阻断，表明体内胺的转运是通过载体介导机制进行的。此外，苯丙胺对DA代谢的抑制作用可被DA摄取抑制剂的预先或延迟处理所逆转或阻断。这些结果支持了胺转运载体在体内的双向功能。
