Kessler J A, Conn G, Hatcher V B
Proc Natl Acad Sci U S A. 1986 May;83(10):3528-32. doi: 10.1073/pnas.83.10.3528.
The choice of which transmitter will be expressed by a neuron is influenced by diffusible differentiating factors produced by a variety of nonneuronal cells. In this study we show that human, bovine, and rat brains contain a soluble heparin-binding factor that stimulates cholinergic and peptidergic expression. We also show that neuronal contact with other cell membranes influences neurotransmitter development and acts synergistically with the effects of the soluble brain factor. Exposure of cultured sympathetic neurons to purified plasma membranes derived either from cultured Schwann cells or from cultured sympathetic neurons promoted expression of choline acetyltransferase (CAT), a cholinergic trait, and of substance P (SP). CAT activity and SP were also stimulated by a 50-kDa soluble protein that was purified 14,000-fold from human, calf, and rat brain by heparin-Sepharose affinity chromatography. CAT activity after concurrent treatment with plasma membranes and the soluble factor far exceeded the sum of the enzyme activities after the individual treatments, suggesting that membrane molecules and the factor facilitated each other. Thus, cell-surface molecules, which have been shown previously to influence neuronal morphogenesis and neurite elongation, may also help determine the transmitter phenotype of the neuron. Moreover, cell-surface molecules may modulate the effects of diffusible differentiating factors.
神经元会表达哪种神经递质，这一选择受多种非神经元细胞产生的可扩散分化因子的影响。在本研究中，我们发现人类、牛和大鼠的大脑中含有一种可溶性肝素结合因子，它能刺激胆碱能和肽能表达。我们还表明，神经元与其他细胞膜的接触会影响神经递质的发育，并与可溶性脑因子的作用协同发挥作用。将培养的交感神经元暴露于源自培养的施万细胞或培养的交感神经元的纯化质膜中，可促进胆碱能特性的胆碱乙酰转移酶（CAT）和P物质（SP）的表达。一种50 kDa的可溶性蛋白也能刺激CAT活性和SP，该蛋白通过肝素-琼脂糖亲和层析从人、小牛和大鼠大脑中纯化了14000倍。同时用质膜和可溶性因子处理后的CAT活性远远超过单独处理后的酶活性之和，这表明膜分子和该因子相互促进。因此, 先前已证明会影响神经元形态发生和神经突伸长的细胞表面分子，也可能有助于确定神经元的递质表型。此外，细胞表面分子可能会调节可扩散分化因子的作用。
