D-1和D-2多巴胺受体激动剂及拮抗剂药物对大鼠基底神经节中[Met5]-脑啡肽、[Leu5]-脑啡肽和神经降压素含量的急性影响。

Acute effects of D-1 and D-2 dopamine receptor agonist and antagonist drugs on basal ganglia [Met5]- and [Leu5]-enkephalin and neurotensin content in the rat.

作者信息

Taylor M D, de Ceballos M L, Jenner P, Marsden C D

机构信息

Parkinson's Disease Society Experimental Research Laboratories, King's College of London, U.K.

出版信息

Biochem Pharmacol. 1991 May 1;41(9):1385-91. doi: 10.1016/0006-2952(91)90112-i.

DOI:10.1016/0006-2952(91)90112-i

PMID:1673340

Abstract

The effects of acute systemic injection of the D-1 agonist SKF 38393 (2.5-20 mg/kg) or the D-1 antagonist SCH 23390 (0.25-2.0 mg/kg), and of the D-2 agonist quinpirole (0.12-1.0 mg/kg) or the D-2 antagonist sulpiride (25-100 mg/kg) on the neuropeptide content of rat basal ganglia were investigated. In striatum, the [Met5]- and [Leu5]-enkephalin content was unaffected by administration of SKF 38393 or SCH 23390. Quinpirole had no effect on [Met5]- and [Leu5]-enkephalin levels but sulpiride produced an increase in both [Met5]- and [Leu5]-enkephalin content. In the nucleus accumbens, SKF 38393 decreased and SCH 23390 increased [Met5]- and [Leu5]enkephalin levels. Quinpirole decreased [Met5]- and [Leu5]-enkephalin levels, while sulpiride decreased [Leu5]-enkephalin levels alone. The content of [Leu5]- but not [Met5]-enkephalin levels in the substantia nigra was increased by administration of SKF 38393, and decreased by SCH 23390. Quinpirole and sulpiride were without effect on the [Met5]- or [Leu5]-enkephalin content of substantia nigra. Neurotensin levels in striatum were increased by administration of SKF 38393 and decreased by SCH 23390. Similarly, quinpirole decreased the neurotensin content while sulpiride caused an increase. In the nucleus accumbens, the neurotensin content was not affected by administration of SKF 38393 but increased by SCH 23390. Neither quinpirole nor sulpiride altered neurotensin levels in the nucleus accumbens. Neurotensin levels in substantia nigra were unaffected by the administration of SKF 38393 and SCH 23390, or by quinpirole and sulpiride. These results indicate that acute administration of D-1 and D-2 agonist and antagonist drugs can alter the levels of [Met5]- and [Leu5]-enkephalin and neurotensin in basal ganglia. However, there are marked differences between brain regions in the regulation of peptide levels by acute D-1 and D-2 receptor occupation.

摘要

研究了急性全身注射D-1激动剂SKF 38393（2.5 - 20毫克/千克）或D-1拮抗剂SCH 23390（0.25 - 2.0毫克/千克），以及D-2激动剂喹吡罗（0.12 - 1.0毫克/千克）或D-2拮抗剂舒必利（25 - 100毫克/千克）对大鼠基底神经节神经肽含量的影响。在纹状体中，[Met5]-和[Leu5]-脑啡肽含量不受SKF 38393或SCH 23390给药的影响。喹吡罗对[Met5]-和[Leu5]-脑啡肽水平无影响，但舒必利使[Met5]-和[Leu5]-脑啡肽含量均增加。在伏隔核中，SKF 38393降低而SCH 23390增加[Met5]-和[Leu5]-脑啡肽水平。喹吡罗降低[Met5]-和[Leu5]-脑啡肽水平，而舒必利仅降低[Leu5]-脑啡肽水平。给予SKF 38393可增加黑质中[Leu5]-脑啡肽水平（但不影响[Met5]-脑啡肽水平），而SCH 23390则使其降低。喹吡罗和舒必利对黑质中[Met5]-或[Leu5]-脑啡肽含量无影响。纹状体中神经降压素水平因SKF 38393给药而升高，因SCH 23390给药而降低。同样，喹吡罗降低神经降压素含量，而舒必利使其升高。在伏隔核中，SKF 38393给药不影响神经降压素含量，但SCH 23390使其升高。喹吡罗和舒必利均未改变伏隔核中的神经降压素水平。SKF 38393和SCH 23390给药，以及喹吡罗和舒必利均未影响黑质中的神经降压素水平。这些结果表明，急性给予D-1和D-2激动剂及拮抗剂药物可改变基底神经节中[Met5]-和[Leu5]-脑啡肽以及神经降压素的水平。然而，急性占据D-1和D-2受体对不同脑区肽水平的调节存在显著差异。