Buu N T
Laboratory of the Autonomic Nervous System, Clinical Research Institute of Montreal, Quebec, Canada.
Biochem Pharmacol. 1989 May 15;38(10):1685-92. doi: 10.1016/0006-2952(89)90318-3.
The possible effects of inhibitors of the two forms of monoamine oxidase (types A and B) on dopamine (DA) and norepinephrine (NE) accumulation and metabolism in the cytoplasmic and microsomal (vesicular) fractions of the rat brain have been examined. It was found that, while L-DOPA treatment raised only cytoplasmic DA without affecting vesicular DA and NE, clorgyline and pargyline treatments caused significant increases in DA and NE concentrations in both cytoplasmic and vesicular fractions. The DA increase in the synaptic vesicles (200-600%) was much more pronounced than that (150%) in the cytoplasm. In contrast, deprenyl treatment increased vesicular DA only slightly without any effect on either vesicular or cytoplasmic NE. L-DOPA administration to rats pretreated with clorgyline and pargyline, but not with deprenyl, further increased cytoplasmic and vesicular DA and NE concentrations. However, excessive increases in vesicular DA lowered vesicular NE. Reserpine drastically reduced vesicular and cytoplasmic DA and NE, and L-DOPA administration to the reserpine-treated rats caused a DA increase only in the cytoplasmic fraction without affecting vesicular DA or NE. The effect of reserpine was abolished by pargyline treatment, which suggests that pargyline may interact with the reserpine-sensitive vesicular uptake. There was a significant correlation between vesicular DA and NE increase.
研究了两种单胺氧化酶(A型和B型)抑制剂对大鼠脑细胞质和微粒体(囊泡)部分中多巴胺(DA)和去甲肾上腺素(NE)积累及代谢的可能影响。结果发现,左旋多巴处理仅提高了细胞质中的DA,而不影响囊泡中的DA和NE,而氯吉兰和帕吉林处理导致细胞质和囊泡部分中的DA和NE浓度显著增加。突触小泡中DA的增加(200%-600%)比细胞质中的增加(150%)更为明显。相比之下,司来吉兰处理仅使囊泡中的DA略有增加,对囊泡或细胞质中的NE均无影响。对预先用氯吉兰和帕吉林而非司来吉兰处理的大鼠给予左旋多巴,可进一步提高细胞质和囊泡中的DA和NE浓度。然而,囊泡中DA的过度增加会降低囊泡中的NE。利血平显著降低了囊泡和细胞质中的DA和NE,对利血平处理的大鼠给予左旋多巴仅使细胞质部分中的DA增加,而不影响囊泡中的DA或NE。帕吉林处理消除了利血平的作用,这表明帕吉林可能与利血平敏感的囊泡摄取相互作用。囊泡中DA和NE的增加之间存在显著相关性。