两种不同的分子，即神经生长因子（NGF）和游离的人氰钴胺素类似肽（free-HCNP），在体外以不同的方式刺激隔核中的胆碱能活性。

Two different molecules, NGF and free-HCNP, stimulate cholinergic activity in septal nuclei in vitro in a different manner.

作者信息

Ojika K, Mitake S, Kamiya T, Kosuge N, Taiji M

机构信息

Second Department of Internal Medicine, Medical School, Nagoya City University, Japan.

出版信息

Brain Res Dev Brain Res. 1994 May 13;79(1):1-9. doi: 10.1016/0165-3806(94)90043-4.

DOI:10.1016/0165-3806(94)90043-4

PMID:8070052

Abstract

Hippocampal cholinergic neurostimulating peptide (HCNP), a novel peptide purified from 10- to 12-day-old rat hippocampus, specifically enhances acetylcholine (AcCho) synthesis in medial septal nuclei in vitro, synthetic de-acetylated HCNP (free-HCNP) elicits more potent enhancement than HCNP. Nerve growth factor (NGF), a neurotrophic substance found in the hippocampus, enhances the cholinergic activity of medial septal nuclei both in vivo and in vitro. The effects of free-HCNP on the development of various cholinergic phenotypes and the interaction of NGF and free-HCNP on cholinergic neurons in vitro were studied. In medial septal nuclei, free-HCNP enhanced AcCho synthesis and choline acetyltransferase (ChoATase) activity and increased Vmax. It did not modulate culture morphology, choline (Cho) uptake, or acetylcholinesterase (AcChoEase) activity. NGF stimulated AcCho synthesis and both ChoATase and AcChoEase activity in the medial septal nuclei and also enhanced AcCho synthesis in a corpus striatum culture. Compared with the effect of either agent alone, the simultaneous application of 3.8 x 10(-11) M NGF and 3 x 10(-11) M free-HCNP (maximal stimulation) to medial septal nucleus culture resulted in a more than additive enhancement of AcCho synthesis, an additive increase in ChoATase activity, and a significant increase in Cho uptake. In corpus striatum and spinal cord cultures, there was no cooperative increase in AcCho synthesis with NGF and free-HCNP nor any enhancement of AcCho synthesis by free-HCNP. These findings suggest that NGF and free-HCNP play a cooperative role during the biochemical differentiation of cholinergic neurons in medial septal nuclei.

摘要

海马胆碱能神经刺激肽（HCNP）是一种从10至12日龄大鼠海马中纯化出的新型肽，在体外可特异性增强内侧隔核中乙酰胆碱（AcCho）的合成，合成的去乙酰化HCNP（游离HCNP）比HCNP引发更强的增强作用。神经生长因子（NGF）是在海马中发现的一种神经营养物质，在体内和体外均可增强内侧隔核的胆碱能活性。研究了游离HCNP对各种胆碱能表型发育的影响以及NGF与游离HCNP在体外对胆碱能神经元的相互作用。在内侧隔核中，游离HCNP增强了AcCho的合成和胆碱乙酰转移酶（ChoATase）的活性，并增加了Vmax。它未调节培养物形态、胆碱（Cho）摄取或乙酰胆碱酯酶（AcChoEase）的活性。NGF刺激内侧隔核中AcCho的合成以及ChoATase和AcChoEase的活性，还增强了纹状体培养物中AcCho的合成。与单独使用任何一种药物的效果相比，将3.8×10⁻¹¹ M NGF和3×10⁻¹¹ M游离HCNP（最大刺激）同时应用于内侧隔核培养物，导致AcCho合成的增强超过相加作用，ChoATase活性呈相加增加，Cho摄取显著增加。在纹状体和脊髓培养物中，NGF和游离HCNP之间没有协同增加AcCho的合成，游离HCNP也没有增强AcCho的合成。这些发现表明，NGF和游离HCNP在内侧隔核胆碱能神经元的生化分化过程中起协同作用。