Avila-Luna Alberto, Prieto-Leyva Jacqueline, Gálvez-Rosas Arturo, Alfaro-Rodriguez Alfonso, Gonzalez-Pina Rigoberto, Bueno-Nava Antonio
División de Neurociencias, Instituto Nacional de Rehabilitación, 'Luis Guillermo Ibarra Ibarra', Secretaría de Salud, Calzada México-Xochimilco 289, Arenal de Guadalupe, C.P. 14389, Mexico City, Mexico.
Neurochem Res. 2015 Jul;40(7):1431-7. doi: 10.1007/s11064-015-1611-4. Epub 2015 May 17.
The striatum is known to possess high levels of D1-like and D2-like receptors (D1Rs and D2Rs, respectively). We have previously shown that selective inhibition of D1Rs increases the dopaminergic metabolic response and proposed that this effect is associated with the concomitant activation of postsynaptic D2Rs by endogenous dopamine (DA). Here, we examined whether activation of D2Rs modulates the metabolism and synthesis of DA in the striatum. We used male Wistar rats to evaluate the effects of the systemic administration of a D2R agonist (bromocriptine), a D1R antagonist (SCH-23390), and the co-administration of these compounds with pargyline on the inhibition of monoamine oxidase. DA and L-3,4-dihidroxyphenylacetic acid (DOPAC) levels and 3,4-dihydroxy-L-phenylalanine (L-DOPA) content were measured using high performance liquid chromatography. The systemic administration of SCH-23390 alone, at 0.25, 0.5, 1 or 2 mg/kg, significantly (P < 0.05) increased DOPAC levels and the DOPAC/DA ratio. At 2, 4 and 8 mg/kg, the administration of bromocriptine alone significantly (P < 0.05) decreased DOPAC levels, L-DOPA content and the DOPAC/DA ratio, whereas at 2 mg/kg, it decreased DA levels. In both groups, co-administration of either SCH-23390 or bromocriptine with pargyline decreased DOPAC levels and the DOPAC/DA ratio by approximately 70 % compared to the levels observed in the control groups. In conclusion, administration of the D2R agonist bromocriptine decreased dopaminergic synthesis and metabolism in the striatum; in contrast, administration of the D1R antagonist SCH-23390 induced the opposite effects.
已知纹状体中D1样和D2样受体(分别为D1R和D2R)水平较高。我们之前已经表明,选择性抑制D1R会增加多巴胺能代谢反应,并提出这种效应与内源性多巴胺(DA)对突触后D2R的伴随激活有关。在此,我们研究了D2R的激活是否会调节纹状体中DA的代谢和合成。我们使用雄性Wistar大鼠来评估全身性给予D2R激动剂(溴隐亭)、D1R拮抗剂(SCH-23390)以及这些化合物与帕吉林联合给药对单胺氧化酶抑制的影响。使用高效液相色谱法测量DA和L-3,4-二羟基苯乙酸(DOPAC)水平以及3,4-二羟基-L-苯丙氨酸(L-DOPA)含量。单独全身性给予0.25、0.5、1或2mg/kg的SCH-23390会显著(P<0.05)增加DOPAC水平和DOPAC/DA比值。单独给予2、4和8mg/kg的溴隐亭会显著(P<0.05)降低DOPAC水平、L-DOPA含量和DOPAC/DA比值,而在2mg/kg时,它会降低DA水平。在两组中,与对照组相比,SCH-23390或溴隐亭与帕吉林联合给药使DOPAC水平和DOPAC/DA比值降低了约70%。总之,给予D2R激动剂溴隐亭会降低纹状体中的多巴胺能合成和代谢;相反,给予D1R拮抗剂SCH-23390会产生相反的效果。