Eva C, Fusco M, Brusa R, Schiavo N, Ricci Gamalero S, Vantini G, Genazzani E
Istituto di Farmacologia e Terapia Sperimentale, Facoltà di Medicina, Torino, Italy.
Neurochem Int. 1994 Jan;24(1):57-65. doi: 10.1016/0197-0186(94)90129-5.
The repeated intracerebroventricular administration of nerve growth factor (5 micrograms/2.5 microliters) to neonatal rats induced the activation of choline acetyltransferase in forebrain cholinergic neurons that was paralleled by a concomitant change in the density of muscarinic cholinergic receptors in the cerebral cortex. The administration of nerve growth factor altered muscarinic binding sites in a biphasic fashion during postnatal development. A significant stimulation of the developmental increase in the density of muscarinic binding sites occurred in nerve growth factor-treated animals at days 2 and 3 after birth. Conversely, nerve growth factor induced a significant decrease in the receptor number at postnatal days 8 and 14. Muscarinic receptor number returned to control values after treatment, suggesting that nerve growth factor-induced changes to muscarinic cholinergic receptors are reversible. Nerve growth factor administration did not affect muscarinic cholinergic receptor density in striatal membranes and did not alter the relative content of cortical messenger RNAs encoding m1 and m3 muscarinic cholinergic receptor subtypes at postnatal day 14, as determined by reverse transcriptase-polymerase chain reaction. The up- and down-regulation of muscarinic cholinergic receptors induced by nerve growth factor during postnatal development may be temporally related events associated with concomitant changes in the activity of choline acetyltransferase.
向新生大鼠反复脑室内注射神经生长因子(5微克/2.5微升)可诱导前脑胆碱能神经元中胆碱乙酰转移酶的激活,同时大脑皮质毒蕈碱型胆碱能受体密度也会发生相应变化。在出生后发育过程中,神经生长因子的注射以双相方式改变毒蕈碱结合位点。在出生后第2天和第3天,神经生长因子处理的动物中,毒蕈碱结合位点密度的发育性增加受到显著刺激。相反,在出生后第8天和第14天,神经生长因子导致受体数量显著减少。处理后毒蕈碱受体数量恢复到对照值,这表明神经生长因子诱导的毒蕈碱型胆碱能受体变化是可逆的。神经生长因子的注射不影响纹状体膜中毒蕈碱型胆碱能受体的密度,并且在出生后第14天,通过逆转录聚合酶链反应测定,也不改变编码m1和m3毒蕈碱型胆碱能受体亚型的皮质信使核糖核酸的相对含量。在出生后发育过程中,神经生长因子诱导的毒蕈碱型胆碱能受体的上调和下调可能是与胆碱乙酰转移酶活性的相应变化相关的时间性事件。