Tanganelli S, Fuxe K, von Euler G, Agnati L F, Ferraro L, Ungerstedt U
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Naunyn Schmiedebergs Arch Pharmacol. 1990 Sep;342(3):300-4. doi: 10.1007/BF00169441.
The interaction of locally perfused cholecystokinin-8 (sulphated) with systemically administered apomorphine was studied on the release of dopamine and its metabolites using microdialysis in the neostriatum of the halothane-anaesthetized male rat. Dialysate levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were assayed by high performance liquid chromatography in combination with electrochemical detection. Perfusion with cholecystokinin-8 (100 microM but not 1 microM or 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC or HVA. At low concentrations (1 microM and 10 nM but not 1 nM), cholecystokinin-8 counteracted the inhibitory effect of apomorphine (0.05 mg/kg, s.c.) on dopamine release. This counteraction was antagonized by perfusion with the cholecystokinin-8 antagonist proglumide (3 microM). At this concentration, proglumide perfused alone was without effect on basal or apomorphine-reduced levels of dopamine. The results indicate a facilitatory effect of cholecystokinin-8 on dopamine release in rat neostriatum only at high concentrations. At lower concentrations, cholecystokinin-8 appears to modulate dopamine release by an inhibitory effect on dopamine autoreceptors possibly involving an intramembrane interaction between presynaptic cholecystokinin-8 receptors and dopamine autoreceptors.
在氟烷麻醉的雄性大鼠新纹状体中，采用微透析技术，研究了局部灌注的胆囊收缩素-8（硫酸化）与全身给药的阿扑吗啡相互作用对多巴胺及其代谢产物释放的影响。通过高效液相色谱结合电化学检测法测定透析液中多巴胺、3,4-二羟基苯乙酸和高香草酸的水平。灌注胆囊收缩素-8（100微摩尔而非1微摩尔或10纳摩尔）可增加多巴胺的透析液水平，而不影响3,4-二羟基苯乙酸或高香草酸的水平。在低浓度时（1微摩尔和10纳摩尔而非1纳摩尔），胆囊收缩素-8可抵消阿扑吗啡（0.05毫克/千克，皮下注射）对多巴胺释放的抑制作用。这种抵消作用可被灌注胆囊收缩素-8拮抗剂丙谷胺（3微摩尔）所拮抗。在此浓度下，单独灌注丙谷胺对多巴胺的基础水平或阿扑吗啡降低的水平无影响。结果表明，胆囊收缩素-8仅在高浓度时对大鼠新纹状体中的多巴胺释放有促进作用。在较低浓度时，胆囊收缩素-8似乎通过对多巴胺自身受体的抑制作用来调节多巴胺释放，这可能涉及突触前胆囊收缩素-8受体与多巴胺自身受体之间的膜内相互作用。
